Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General Procedure for Cascade Cycloaddition Reaction
3.2. Gram-Scale Synthesis of Compound 3aa
3.3. Chemical Transformations of 3ba, 3aa, and 3cg
3.4. Charaterization of 3 Products
- 5-acetyl-3-methyl-1,4-diphenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3aa): White solid (yield: 42.0 mg, 98%). M.P. = 152.9–153.1 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 7.7 Hz, 2H), 7.54–7.48 (br, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.4 Hz, 3H), 7.28–7.25 (br, 1H)), 7.20–7.14 (br, 1H), 5.12 (s, 1H), 3.92–3.81 (m, 1H), 3.50–3.38 (m, 1H), 2.68–2.56 (m, 1H), 2.47–2.24 (m, 3H), 2.16 (s, 3H), 1.56 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.3, 169.4, 148.9, 145.3, 138.6, 135.8, 128.8, 128.0, 127.7, 126.3, 122.6, 119.8, 100.2, 93.4, 47.5, 42.8, 35.4, 26.7, 25.0, 14.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H23N3O4 430.1761; Found 430.1759.
- 5-acetyl-4-(4-bromophenyl)-3-methyl-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ab): White solid (yield: 37.0 mg, 73%). M.P. = 93.7–93.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.7 Hz, 2H), 7.47 (s, 1H), 7.46 (s, 2H), 7.44 (s, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 5.12 (s, 1H), 3.93–3.84 (m, 1H), 3.47–3.38 (m, 1H), 2.67–2.56 (m, 1H), 2.46–2.25 (m, 3H), 2.59 (s, 3H), 1.60 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.1, 169.3, 148.6, 145.3, 138.5, 135.2, 131.2, 131.1, 128.8, 126.4, 122.6, 121.8, 120.0, 99.7, 93.2, 46.4, 43.0, 35.5, 26.5, 25.1, 14.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22BrN3O4 508.0866; Found 508.0867.
- 5-acetyl-3-methyl-4-(4-nitrophenyl)-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ac): White solid (yield: 30.8 mg, 65%). M.P. = 109.9–110.3 °C; 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 7.6 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.63 (dd, J = 8.7, 1.2 Hz, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.36–7.27 (m, 2H), 5.30 (s, 1H), 3.92–3.86 (m, 1H), 3.49–3.42 (m, 1H), 2.67–2.62 (m, 1H), 2.48–2.34 (m, 3H), 2.21 (s, 3H), 1.58 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 197.9, 169.1, 148.2, 147.2, 145.4, 144.2, 138.4, 132.7, 130.6, 129.0, 126.7, 123.1, 122.7, 120.5, 99.2, 93.2, 46.3, 43.1, 35.5, 26.2, 25.2, 14.3ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22N4O6 475.1612; Found 475.1631.
- 5-acetyl-4-(4-methoxyphenyl)-3-methyl-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ad): White solid (yield:37.6 mg, 82%). M.P. = 87.7–88.1 °C; 1H NMR (400 MHz, CDCl3): δ7.63 (dd, J = 8.7, 1.2 Hz, 2H), 7.45 (t, J = 7.5 Hz, 2H), 7.40 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 7.7 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 6.82 (t, J = 4.4 Hz 2H), 5.06 (s, 1H), 3.90–3.83 (m, 1H), 3.80 (s, 3H), 3.45–3.39 (m, 1H), 2.65–2.58 (m, 1H), 2.42–2.31 (m, 3H), 2.16 (s, 3H), 1.58 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.6, 169.5, 159.0, 149.0, 145.2, 138.7, 132.5, 130.7, 128.9, 127.6, 126.3, 122.6, 119.6, 113.7, 113.1, 100.4, 93.4, 55.1, 46.9, 42.8, 35.5, 26.8, 25.0, 14.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H25N3O5 460.1867; Found 460.1864.
- 5-acetyl-3-methyl-4-(naphthalen-2-yl)-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ae): White solid (yield: 35.9 mg, 75%). M.P. = 168.5–168.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.89–7.68 (m, 3H), 7.51–7.47 (m, 3H), 7.48 (t, J = 7.4 Hz, 4H), 7.33 (t, J = 7.4 Hz, 2H), 5.36 (s, 1H), 3.90–3.85 (m, 1H), 3.49–3.42 (m, 1H), 2.66–2.59 (m, 1H), 2.48–2.24 (m, 3H), 2.16 (s, 3H), 1.53 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.6, 198.3, 169.5, 148.9, 145.4, 138.7, 132.8, 128.9, 128.1, 127.7, 127.6, 126.4, 126.1, 126.0, 122.6, 119.8, 99.8, 93.2, 47.6, 42.9, 35.5, 26.8, 25.0, 14.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H25N3O4 480.1917; Found 480.1922.
- 5-acetyl-1-(4-chlorophenyl)-3-methyl-4-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3af): White solid (yield: 33.3 mg, 72%). M.P. = 143.2–143.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.60 (dd, J = 8.8, 2.0 Hz, 2H), 7.51–7.47 (br, 1H), 7.41 (dt, J = 8.9, 2.7 Hz, 2H), 7.34–7.22 (br, 3H), 7.18–7.08 (br, 1H), 5.12 (s, 1H), 3.91–3.81 (m, 1H), 3.46–3.37 (m, 1H), 2.64–2.56 (m, 1H), 2.42–2.56 (m, 3H), 2.16 (s, 3H), 1.55 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.2, 169.3, 149.3, 145.4, 137.2, 135.6, 131.7, 131.5, 128.9, 128.0, 127.8, 123.6, 119.8, 100.4, 93.4, 47.4, 42.9, 35.5, 26.7, 25.0, 14.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22ClN3O4 464.1371; Found 464.1369.
- 5-acetyl-3-methyl-4-phenyl-1-(p-tolyl)-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ag): White solid (yield: 35.4 mg, 80%). M.P. = 149.2–149.6 °C; 1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 3H), 7.36–7.26 (br, 2H), 7.26 (t, J = 7.8 Hz, 3H), 7.21–7.12 (br, 1H), 5.12 (s, 1H), 3.90–3.82 (m, 1H), 3.45–3.37 (m, 1H), 2.65–2.55 (m, 1H), 2.41 (s, 3H), 2.40–2.25 (m, 3H), 2.15 (s, 3H), 1.55 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.5, 169.4, 148.6, 145.3, 136.2, 135.9, 131.5, 129.7, 129.4, 128.6, 127.7, 122.7, 120.0, 100.0, 93.5, 47.6, 42.8, 35.5, 26.8, 25.0, 21.1, 14.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H25N3O4 444.1917; Found 444.1920.
- 5-acetyl-1,3,4-triphenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ah): White solid (yield: 42.2 mg, 86%). M.P. = 76.2–76.6 °C; 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 5.7 Hz, 2H), 7.49 (t, J = 8.3 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 7.14–7.01 (m, 7H), 6.99 (d, J = 1.8 Hz, 3H), 5.39 (s, 1H), 3.90–3.82 (m, 1H), 3.48–3.39 (m, 1H), 2.67–2.55 (m, 1H), 2.46–2.25 (m, 3H), 2.14 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ198.5, 169.4, 152.0, 145.7, 138.7, 135.6, 133.7, 128.9, 128.5, 127.5, 127.4, 127.2, 126.7, 123.0, 119.9, 100.7, 93.9, 47.4, 42.9, 35.5, 26.8, 25.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H25N3O4 492.1918; Found 492.1932.
- 3-methyl-1,4-diphenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3ba): White solid (yield: 29.8 mg, 77%). M.P. = 146.8–147.0 °C; 1H NMR (400 MHz, CDCl3): δ7.64 (d, J = 7.9 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.40–7.32 (m, 4H), 7.30–7.26 (m, 2H), 4.78 (dd, J = 13.6, 6.6 Hz, 2H), 3.78–3.71 (m, 1H), 3.35–3.29 (m, 1H), 2.55–2.51 (m, 1H), 3.34–2.21 (m, 3H), 1.61 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 171.0, 148.6, 146.5, 138.7, 135.0, 129.5, 129.5, 128.9, 128.8, 128.8, 128.5, 128.3, 128.0, 126.4, 122.7, 122.5, 120.8, 99.8, 86.1, 47.8, 42.2, 35.1, 24.8, 14.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21N3O3 388.1656; Found 388.1622.
- 5-acetyl-3-methyl-1,4-diphenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3ca): White solid (yield: 31.0 mg, 70%). M.P. = 213.7–213.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 7.6 Hz, 2H), 7.16 (t, J = 7.6 Hz, 2H), 7.35–7.21 (m, 6H), 4.80 (s, 1H), 3.89 (dd, J = 13.3, 4.6 Hz, 1H), 2.76 (d, J = 12.8 Hz, 1H), 2.55 (td, J = 12.9, 3.0 Hz, 1H), 2.00–1.95 (br, 1H), 1.99 (s, 3H), 1.93 (s, 3H), 1.90–1.83 (m, 1H), 1.82–1.70 (m, 2H), 1.53–1.39 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.5, 165.5, 148.3, 145.1, 138.3, 136.7, 129.7, 128.9, 128.4, 127.7, 126.6, 122.4, 110.4, 101.2, 91.9, 48.0, 38.9, 34.4, 27.4, 23.3, 20.8, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H25N3O4 444.1918; Found 444.1872.
- 5-acetyl-3-methyl-1,4-diphenyl-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3da): White solid (yield: 34.2 mg, 75%). M.P. = 195.0–195.3 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 7.7 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.34–7.21 (m, 6H), 4.79 (s, 1H), 3.85 (d, J = 13.9 Hz, 1H), 2.90–2.79 (m, 2H), 2.40–2.31 (m, 1H), 1.98 (s, 3H), 1.96 (s, 3H) 1.94–1.85 (m, 2H), 1.78–1.69 (br, 1H), 1.53–1.33 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.6, 166.4, 148.1, 145.3, 138.4, 136.9, 129.6, 128.9, 128.4, 127.7, 126.5, 122.5, 115.4, 100.8, 91.6, 48.0, 40.5, 38.4, 29.5, 28.5, 27.6, 22.5, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H27N3O4 458.2074; Found 458.2039.
- 5-acetyl-3-methyl-1,4-diphenyl-4,5,8,9,10,11,12,13-octahydro-5,13a-epoxyazocino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3ea): White solid (yield: 38.6 mg, 82%). M.P. = 149.5–149.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 7.7 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.34–7.21 (m, 6H), 4.80 (s, 1H), 3.70 (dt, J = 14.3, 4.0 Hz, 1H), 2.80 (td, J = 11.9, 3.6 Hz, 1H), 2.66 (dt, J = 16.1, 4.4 Hz, 1H), 2.50 (td, J = 10.8, 4.4 Hz, 1H), 1.98 (s, 3H), 1.96 (s, 3H), 1.86–1.75 (m, 3H), 1.70–1.55 (m, 3H), 1.53–1.35 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.6, 167.0, 148.2, 145.2, 138.5, 136.8, 129.6, 128.9, 128.4, 127.7, 126.4, 122.3, 114.1, 100.9, 91.4, 48.4, 40.4, 31.7, 27.6, 27.0, 25.0, 23.8, 22.1, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H29N3O4 472.2230; Found 472.2236.
- 5-acetyl-3,7,8-trimethyl-1,4-diphenyl-4,5,7,8-tetrahydro-5,8-epoxypyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3fa): White solid (yield: 14.6 mg, 35%). M.P. = 192.5–192.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (dd, J = 8.7, 1.2 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.38–7.25 (m, 6H), 4.80 (s, 1H), 2.76 (s, 3H), 2.09 (s, 3H), 1.98 (s, 3H), 1.93 (s, 3H), ppm; 13C NMR (100 MHz, CDCl3): δ 200.2, 167.3, 148.2, 145.1, 138.3, 136.7, 129.7, 129.0, 128.4, 127.7, 126.6, 122.4, 112.5, 101.0, 91.8, 48.1, 27.3, 25.9, 23.0, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23N3O4 418.1761; Found 418.1767.
- 4-(4-bromophenyl)-3-methyl-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bb): White solid (yield: 41.8 mg, 90%). M.P. = 106.6–106.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.8 Hz, 2H), 7.53 (dd, J = 8.1, 1.8 Hz, 1H), 7.50–7.41 (m, 3H), 7.31 (d, J = 7.4 Hz, 1H), 7.25 (dd, J = 8.0, 2.0 Hz, 1H), 7.15 (dd, J = 8.4, 2.1 Hz, 1H), 4.74 (dd, J = 14.9, 6.6 Hz, 2H), 3.78–3.69 (m, 1H), 3.35–3.27 (m, 1H), 2.57–2.45 (m, 1H), 2.36–2.21 (m, 3H), 1.63 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 170.8, 148.3, 146.5, 138.6, 134.2, 131.7, 131.6, 131.3, 131.0, 128.9, 126.5, 122.7, 122.0, 120.9, 99.3, 85.7, 47.2, 42.2, 35.0, 26.9, 24.8, 15.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H20BrN3O3 466.0760; Found 466.0769.
- 3-methyl-4-(4-nitrophenyl)-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bc): White solid (yield: 34.5 mg, 80%). M.P. = 122.3–122.7 °C; 1H NMR (400 MHz, CDCl3): δ 8.28 (dd, J = 8.3, 2.2 Hz, 1H), 8.20 (dd, J = 8.3, 2.2 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.56 (dd, J = 8.4, 1.4 Hz, 1H), 7.46 (t, J = 7.4 Hz, 3H), 7.33 (t, J = 7.4 Hz, 1H), 4.93 (d, J = 6.6 Hz, 1H), 4.77 (d, J = 6.6 Hz, 1H), 3.80–3.69 (m, 1H), 3.38–3.27 (m, 1H), 2.57–2.45 (m, 1H), 2.36–2.21 (m, 3H), 1.62 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 171.2, 159.2, 148.7, 146.4, 138.7, 130.6, 130.5, 129.0 128.9 128.8, 127.0, 126.3, 122.7, 122.4, 120.7, 114.1, 113.8, 113.8, 100.1, 86.2, 55.2, 47.0, 42.1, 35.0, 24.8, 14.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H20N4O5 433.1506; Found 433.1510.
- 3-methyl-1-phenyl-4-(3,4,5-trimethoxyphenyl)-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bl): White solid (yield: 36.7 mg, 77%). M.P. = 89.7–90.0 °C; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.7 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 7.4 Hz, 1H), 6.54 (dd, J = 28.8, 1.6, Hz, 2H), 4.73 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 3.91 (s, 3H), 3.89 (s, 3H), 3.78 (s, 3H), 3.76–3.69 (m, 1H), 3.39–3.30 (m, 1H), 2.54–2.48 (m, 1H), 2.35–2.20 (m, 3H), 1.67 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 171.2, 153.3, 153.0 148.6, 146.5, 138.7, 137.7, 130.6, 128.8, 126.4, 122.6, 122.4, 120.6, 107.1, 106.8, 100.0, 86.0 61.0, 56.4, 56.2, 48.3, 42.3, 35.0, 24.9, 14.8 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H27N3O6478.1972; Found 478.1980.
- 3-methyl-1-phenyl-4-(4-(trifluoromethyl)phenyl)-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bm): White solid (yield: 40.0 mg, 88%). M.P. = 168.7–168.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.70 -7.56 (m, 4H),7.52–7.42 (m, 3H), 7.40 (d, J = 8.2 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 4.87 (d, J = 6.6 Hz, 1H), 4.76 (d, J = 6.6 Hz, 1H), 3.80–3.69 (m, 1H), 3.39–3.28 (m, 1H), 2.57–2.48 (m, 1H), 2.35–2.20 (m, 3H), 1.60 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 170.6, 148.1, 146.6, 139.3, 138.6, 130.3, 130.0, 130.0, 129.7, 128.9, 126.6, 125.6, 125.3, 125.3, 122.8, 121.0, 99.0, 85.7, 47.6, 42.2, 35.0, 26.9, 24.8, 15.0 ppm; 19F NMR (376 MHz, CDCl3): δ 62.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H20F3N3O3 456.1529; Found 456.1534.
- 4-(2-methoxyphenyl)-3-methyl-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bn): White solid (yield: 38.7 mg, 93%). M.P. = 158.2–158.5 °C; 1H NMR (400 MHz, CDCl3): δ7.66 (d, J = 7.6 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.34–7.26 (m, 2H), 7.18 (dd, J = 7.6, 1.5 Hz, 1H), 6.95 (t, J = 7.6 Hz, 2H), 5.35 (d, J = 7.0 Hz, 1H), 4.91 (d, J = 7.0 Hz, 1H), 3.93 (s, 3H), 3.78–3.65 (m, 1H), 3.35–3.27 (m, 1H), 2.57–2.46 (m, 1H), 2.35–2.17 (m, 3H), 1.69 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 171.5, 156.8, 148.6, 146.9, 138.9, 130.5, 129.5, 128.8, 128.5, 126.2, 123.1, 122.6, 122.4, 122.3, 121.6, 120.9, 120.6, 120.4, 110.1, 99.7, 87.0, 84.1, 55.4, 42.1, 39.4, 35.2, 24.8, 14.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23N3O4 418.1761; Found 418.1763.
- 3,4,4-trimethyl-1-phenyl-4,5,9,10-tetrahydro-8H-5,10a-epoxypyrazolo[4,3-g]pyrrolo[2,1-b][1,3]oxazocin-6(1H)-one (3bo): White solid (yield: 32.2 mg, 95%). M.P. = 94.4–94.9 °C; 1H NMR (400 MHz, CDCl3): δ7.54 (dd, J = 8.7, 1.2 Hz, 2H), 7.40 (t, J = 8.2 Hz, 2H), 7.27 (d, J = 7.2 Hz, 1H), 4.25 (s, 1H), 3.77–3.56 (m, 1H), 3.30–3.06 (m, 1H), 2.50–2.40 (m, 1H), 2.37 (s, 3H), 2.29–2.17 (m, 3H), 1.57 (s, 3H), 1.41 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 171.7, 146.9, 144.7, 138.6, 128.7, 126.4, 123.0, 120.0, 105.9, 92.2, 41.5, 39.5, 34.4, 28.6, 24.9, 22.1, 16.5 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H21N3O3 340.1656; Found 340.1660.
- 5-acetyl-3-methyl-4-(4-nitrophenyl)-1-phenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cc): White solid (yield: 39.0 mg, 80%). M.P. = 231.6–231.9 °C); 1H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 4.95 (s, 1H), 3.91 (dd, J = 13.2, 4.5 Hz, 1H), 2.79 (d, J = 13.2 Hz, 1H), 2.56 (td, J = 13.0, 3.0 Hz, 1H), 2.03 (d, J = 13.5 Hz, 1H), 1.98 (s, 6H), 1.91 (dd, J = 13.3, 4.1 Hz, 1H), 1.86–1.68 (m, 2H), 1.56–1.42 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.0, 164.9, 147.9, 147.4, 145.2, 144.5, 138.0, 130.8, 129.0, 126.9, 123.5, 122.5, 110.8, 100.2, 91.5, 46.8, 39.2, 34.4, 27.2, 23.2, 20.8, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H24N4O6 489.1768; Found 489.1773.
- 5-acetyl-4-(4-methoxyphenyl)-3-methyl-1-phenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cd): White solid (yield: 42.5 mg, 90%). M.P. = 155.4–155.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 7.6 Hz, 2H), 7.50 (t, J = 5.8 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H), 7.23 (d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 4.76 (s, 1H), 3.87 (dd, J = 13.3, 4.6 Hz, 1H), 3.77 (s, 3H), 2.75 (d, J = 13.2 Hz, 1H), 2.55 (td, J = 13.0, 3.0 Hz, 1H), 2.03–1.99 (m, 1H), 1.98 (s, 3H), 1.94 (s, 3H), 1.86 (dd, J = 13.3, 4.1 Hz, 1H), 1.82–1.67 (m, 2H), 1.52–1.41 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.7, 165.5, 158.9, 148.3, 145.0, 138.3, 130.7, 128.9, 128.8, 126.5, 122.4, 113.7, 110.3, 101.4, 92.0, 55.2, 47.3, 38.9, 34.4, 27.5, 23.2, 20.8, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H27N3O5 474.2023; Found 474.2032.
- 5-acetyl-3-methyl-4-(naphthalen-2-yl)-1-phenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3ce): White solid. (yield: 46.8 mg, 95%). M.P. = 202.2–202.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.87 -7.78 (m, 2H), 7.77 (t, J = 4.5 Hz, 2H), 7.71 (d, J = 7.6 Hz, 2H), 7.52–7.45 (m, 5H), 7.33 (t, J = 7.4 Hz, 1H), 5.00 (s, 1H), 3.93 (dd, J = 13.3, 4.6 Hz, 1H), 2.81 (d, J = 13.2 Hz, 1H), 2.60 (td, J = 13.0, 3.0 Hz, 1H), 2.06–2.01 (m, 1H), 2.00 (s, 3H), 1.92 (s, 3H), 1.89 (d, J = 3.8 Hz, 1H), 1.86–1.74 (m, 2H), 1.55–1.43 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.5, 165.5, 148.4, 145.2, 138.3, 134.3, 133.0, 132.8, 129.0, 128.8, 128.2, 128.1, 127.6, 127.4, 126.6, 126.2, 126.1, 122.4, 110.5, 101.2, 92.1, 48.0, 39.0, 34.5, 27.5, 23.3, 20.9, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H27N3O4 494.2074; Found 494.2079.
- 5-acetyl-1-(4-chlorophenyl)-3-methyl-4-phenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cf): White solid (yield: 38.1 mg, 80%). M.P. = 113.3–113.7 °C; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 7.33–7.22 (m, 5H), 4.80 (s, 1H), 3.89 (dd, J = 13.3, 4.6 Hz, 1H), 2.76 (d, J = 13.2 Hz, 1H), 2.52 (td, J = 13.0, 3.0 Hz, 1H), 2.08 (d, J = 13.4 Hz, 1H), 1.98 (s, 3H), 1.94 (s, 3H), 1.92–1.64 (m, 3H), 1.57–1.39 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.3, 165.4, 148.7, 145.2, 136.9, 136.5, 132.0, 129.6, 129.1, 128.4, 127.7, 123.3, 110.6, 101.5, 91.8, 48.0, 39.0, 34.4, 27.4, 23.2, 20.9, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H24ClN3O4 478.1528; Found 478.1532.
- 5-acetyl-3-methyl-4-phenyl-1-(p-tolyl)-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cg): White solid (yield: 38.3 mg, 84%). M.P. = 144.7–148.1 °C; 1H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 8.4 Hz, 2H), 7.31 (td, J = 8.5, 1.6 Hz, 2H), 7.29–7.22 (m, 5H), 4.80 (s, 1H), 3.89 (dd, J = 13.3, 4.6 Hz, 1H), 2.75 (d, J = 13.2 Hz, 1H), 2.52 (td, J = 13.0, 3.0 Hz, 1H), 2.41 (s, 3H), 2.04–1.99 (m, 1H), 1.98 (s, 3H), 1.94 (s, 3H), 1.92–1.68 (m, 3H), 1.53–1.39 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.6, 165.5, 147.9, 145.0, 136.8, 136.4, 135.8, 129.7, 129.5, 128.3, 127.6, 122.4, 110.3, 101.0, 91.9, 48.0, 38.9, 34.4, 27.4, 23.3, 21.1, 20.8, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H27N3O4 458.2074; Found 458.2079.
- 5-acetyl-3-methyl-1-phenyl-4-(3,4,5-trimethoxyphenyl)-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cl): White solid (yield: 39.9 mg, 75%). M.P. = 238.3–238.7 °C; 1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 7.6 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.4 Hz, 1H), 6.54 (s, 2H), 4.74 (s, 1H), 3.89 (dd, J = 13.3, 4.6 Hz, 1H), 3.83 (s, 6H), 3.82 (s, 3H), 2.74 (d, J = 13.2 Hz, 1H), 2.57 (td, J = 13.0, 3.0 Hz, 1H), 2.04 (s, 3H), 1.98 (s, 3H), 1.90 (td, J = 13.1, 3.9 Hz, 1H), 1.85–1.66 (m, 1H),1.56–1.41 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.6, 165.4, 152.8, 148.4, 145.0, 138.3, 137.5, 132.4, 129.0, 126.6, 122.4, 110.4, 106.9, 101.0, 91.9, 60.8, 56.2, 48.2, 39.0, 34.4, 27.6, 23.2, 20.8, 13.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H31N3O7534.2234; Found 534.2234.
- 5-acetyl-4-(2-methoxyphenyl)-3-methyl-1-phenyl-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cn): White solid (yield: 40.6 mg, 86%). M.P. = 162.3–162.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 7.6 Hz, 2H), 7.45 (t, J = 5.8 Hz, 3H), 7.30 (t, J = 7.4 Hz, 1H), 7.21 (td, J = 8.5, 1.6 Hz, 1H), 6.88 (m, 2H), 5.51 (s, 1H), 3.92 (s, 3H), 3.89 (dd, J = 13.3, 4.6 Hz, 1H), 2.74 (d, J = 13.2 Hz, 1H), 2.56 (td, J = 13.0, 3.0 Hz, 1H), 2.20 (s, 3H), 2.00 (s, 3H), 1.96–1.87 (m, 2H), 1.81–1.68 (m, 2H), 1.52–1.37 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.9, 166.2, 155.5, 148.4, 145.1, 138.4 130.9, 129.0, 128.9, 126.4, 125.3, 122.4, 121.0, 110.5, 110.2, 102.1, 92.0, 55.5, 39.1, 38.8, 34.4, 26.8, 23.2, 20.8, 12.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H27N3O5. 474.2023; Found 474.2026.
- 5-acetyl-3-methyl-1-phenyl-4-(thiophen-2-yl)-4,5,8,9,10,11-hexahydro-5,11a-epoxypyrazolo[4,3-g]pyrido[2,1-b][1,3]oxazocin-6(1H)-one (3cp): White solid (yield: 38.1 mg, 85%). M.P. = 181.6–181.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.7 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.19 (d, J = 5.0 Hz, 1H), 6.96 (d, J = 3.0 Hz, 1H), 6.90 (t, J = 14.0 Hz, 2H), 5.17 (s, 1H), 3.87 (dd, J = 13.3, 4.6 Hz, 1H), 2.76 (d, J = 13.2 Hz, 1H), 2.52 (td, J = 13.0, 3.0 Hz, 1H), 2.10 (s, 3H), 2.09 (s, 3H), 2.04–1.84 (m, 2H), 1.82–1.65 (m, 2H), 1.54–1.39 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.3, 164.9, 148.2, 144.4, 139.9, 138.2, 128.9, 127.2, 126.7, 126.5, 125.7, 122.5, 110.5, 101.3, 91.7, 43.1, 39.0, 34.4, 27.3, 23.2, 20.8, 12.8 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23N3O4S 450.1482; Found 450.1486.
- 5-acetyl-4-(4-bromophenyl)-3-methyl-1-phenyl-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3db): White solid (yield: 32.1 mg, 60%). M.P. = 212.0–212.2 °C; 1H NMR (400 MHz, CDCl3): δ7.63 (d, J = 7.5 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H),7.32 (t, J = 7.4 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H), 4.77 (s, 1H), 3.86 (dd, J = 13.3, 4.6 Hz, 1H), 2.91–2.75 (m, 2H), 2.37–2.29 (m, 1H), 2.00 (s, 3H), 1.97 (s, 3H), 1.96–1.88 (m, 2H), 1.79–1.71 (m, 1H), 1.54–1.39 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.5, 166.1, 148.0, 145.3, 138.3, 136.1, 131.5, 131.4, 129.0, 126.6, 122.5, 121.8, 115.6, 100.3, 91.4, 47.1, 40.6, 38.4, 29.5, 28.5, 27.7, 22.6, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H26BrN3O4 536.1179; Found 536.1189.
- 5-acetyl-4-(4-methoxyphenyl)-3-methyl-1-phenyl-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3dd): White solid (yield: 37.9 mg, 78%). M.P. = 161.0–161.4 °C; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.5 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.5 Hz, 1H),7.22 (dd, J = 8.7, 1.9 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 4.75 (s, 1H), 3.84 (d, J = 10.6 Hz, 1H), 3.77 (s, 3H), 2.92–2.74 (m, 2H), 2.40–2.30 (m, 1H), 1.97 (s, 6H), 1.96–1.88 (m, 2H), 1.81–1.71 (m, 1H), 1.54–1.27 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.8, 166.4, 158.9, 148.1, 145.2, 138.5, 130.7, 128.9, 126.5, 122.5, 115.4, 113.7, 100.9, 91.7, 55.2, 47.4, 40.5, 38.4, 29.5, 28.5, 27.7, 22.5, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H29N3O5 488.2180; Found 488.2187.
- 5-acetyl-3-methyl-4-(naphthalen-1-yl)-1-phenyl-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3de): White solid (yield: 46.1 mg, 91%). M.P. = 183.5–183.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.86–7.78 (m, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 7.6 Hz, 2H), 7.52–7.41 (m, 5H), 7.32 (t, J = 7.4 Hz, 2H), 4.98 (s, 1H), 3.89 (d, J = 10.6 Hz, 1H), 2.98–2.77 (m, 2H), 2.40–2.30 (m, 1H), 1.99 (s, 3H), 1.98–1.94 (br, 1H), 1.95 (s, 3H), 1.94–1.91 (br, 1H), 1.81–1.71 (m, 1H), 1.54–1.27 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.5, 166.4, 148.3, 145.4, 138.5, 134.5, 133.0, 132.8, 129.0, 128.8, 128.2, 128.1, 127.6, 127.3, 126.5, 126.1, 126.1, 122.5, 115.5, 100.7, 91.8, 48.1, 40.6, 38.4, 29.6, 28.5, 27.7, 22.6, 13.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C31H29N3O4 508.2230; Found 508.2239.
- 5-acetyl-3-methyl-4-phenyl-1-(p-tolyl)-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3dg): White solid (yield: 42.3 mg, 90%). M.P. = 191.0–191.4 °C; 1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 2H), 7.30 (t, J = 6.8 Hz, 3H), 7.27–7.21 (m, 4H), 4.79 (s, 1H), 3.84 (d, J = 14.0 Hz, 1H), 2.90–2.74 (m, 2H), 2.40 (s, 3H), 2.34 (dd, J = 15.6, 10.6 Hz, 1H), 1.97 (s, 3H), 1.96 (s, 3H), 1.94–1.86 (m, 2H), 1.77–1.70 (br, 1H), 1.51–1.38 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.7, 166.4, 147.8, 145.2, 137.0, 136.3, 136.0, 129.6, 129.5, 128.3, 127.6, 122.5, 115.3, 100.6, 91.6, 48.0, 40.5, 38.4, 29.5, 28.5, 27.6, 22.5, 21.1, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H29N3O4 472.2230; Found 472.2236.
- 5-acetyl-3-methyl-1-phenyl-4-(3,4,5-trimethoxyphenyl)-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3dl): White solid (yield: 44.8 mg, 82%). M.P. = 215.2–215.5 °C; 1H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 7.6 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H), 6.52 (s, 2H), 4.71 (s, 1H), 3.89–3.82 (br, 1H), 3.81 (s, 6H), 3.80 (s, 3H), 2.89–2.74 (m, 2H), 2.35 (dd, J = 15.6, 10.6 Hz, 1H), 2.02 (s, 3H), 1.99 (s, 3H), 1.96–1.86 (m, 2H), 1.77–1.69 (m, 1H), 1.51–1.32 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.7, 166.3, 152.8, 148.2, 145.2, 138.4, 137.4, 132.5, 129.0, 126.6, 122.4, 115.5, 106.8, 100.6, 91.6, 60.8, 56.2, 48.3, 40.6, 38.4, 29.5, 28.5, 27.8, 22.6, 13.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H33N3O7 548.2391; Found 548.2404.
- 5-acetyl-4-(2-methoxyphenyl)-3-methyl-1-phenyl-4,5,9,10,11,12-hexahydro-8H-5,12a-epoxyazepino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3dn): White solid (yield: 39.4 mg, 81%). M.P. = 190.9–191.3 °C; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 6.9 Hz, 3H), 7.28 (t, J = 7.4 Hz, 1H), 7.20 (td, J = 8.7, 1.9 Hz, 1H), 6.88 (t, J = 6.1 Hz, 2H), 5.53 (s, 1H), 3.92 (s, 3H), 3.85 (dd, J = 10.6, 3.0 Hz, 1H), 2.96–2.74 (m, 2H), 2.37–2.27 (m, 1H), 2.26 (s, 3H), 2.00 (s, 3H), 1.96–1.88 (m, 2H), 1.81–1.71 (m, 1H), 1.54–1.27 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 199.0, 167.2, 155.4, 148.3, 145.2, 138.5, 130.9, 129.0, 128.9, 126.4, 125.5, 122.5, 121.1, 115.3, 110.5, 101.7, 91.8, 55.4, 40.4, 38.8, 38.2, 29.5, 28.5, 26.8, 22.4, 12.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H29N3O5 488.2180; Found 488.2186.
- 5-acetyl-4-(4-methoxyphenyl)-3-methyl-1-phenyl-4,5,8,9,10,11,12,13-octahydro-5,13a-epoxyazocino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3ed): White solid (yield: 42.5 mg, 85%). M.P. = 106.5–106.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 11.6 Hz, 2H), 4.75 (s, 1H), 3.76 (s, 3H), 3.85 (dt, J = 14.4, 4.0 Hz, 1H), 2.78 (td, J = 11.9, 3.5 Hz, 1H), 2.64 (dt, J = 15.7, 4.3 Hz, 1H), 2.48 (td, J = 10.9, 4.3 Hz, 1H), 1.98 (s, 3H), 1.97 (s, 3H), 1.86–1.71 (m, 3H), 1.70–1.55 (m, 3H), 1.54–1.33 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 200.8, 167.0, 158.9, 148.1, 145.1, 138.5, 130.7, 128.9, 128.8, 126.4, 122.3, 114.1, 113.7, 101.1, 91.6, 55.2, 47.7, 40.3, 31.7, 27.7, 27.0, 25.0, 23.8, 22.1, 12.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H31N3O5 502.2336; Found 502.2341.
- 5-acetyl-3-methyl-1-phenyl-4-(3,4,5-trimethoxyphenyl)-4,5,8,9,10,11,12,13-octahydro-5,13a-epoxyazocino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3el): White solid (yield: 51.0 mg, 90%). M.P. = 223.2–223.6 °C; 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 7.8 Hz, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 2H), 6.50 (s, 2H), 4.71 (s, 1H), 3.81 (s, 6H), 3.80 (s, 3H), 3.64 (dt, J = 14.4, 3.9 Hz, 1H), 2.76 (td, J = 11.9, 3.5 Hz, 1H), 2.60 (dt, J = 15.7, 4.3 Hz, 1H), 2.53–2.41 (m, 1H), 2.01 (s, 3H), 1.98 (s, 3H), 1.84–1.70 (m, 3H), 1.68–1.53 (m, 3H), 1.52–1.35 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ200.7, 166.9, 152.8, 148.2, 145.1, 138.4, 137.4, 132.4, 129.0, 126.5, 122.2, 114.2, 106.8, 100.8, 91.4, 60.8, 56.2, 48.5, 40.4, 31.8, 27.8, 27.0, 25.0, 23.8, 22.1, 13.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C31H35N3O7 562.2547; Found 562.2556.
- 5-acetyl-4-(2-methoxyphenyl)-3-methyl-1-phenyl-4,5,8,9,10,11,12,13-octahydro-5,13a-epoxyazocino[2,1-b]pyrazolo[4,3-g][1,3]oxazocin-6(1H)-one (3en): White solid (yield: 25.0 mg, 50%). M.P. = 69.6–69.9 °C; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.7 Hz, 3H), 7.28 (t, J = 7.4 Hz, 1H), 7.21 (td, J = 8.4, 1.6 Hz, 1H), 6.92–6.85 (m, 2H), 5.51 (s, 1H), 3.93 (s, 3H), 3.67 (dt, J = 14.4, 4.0 Hz, 1H), 2.80 (td, J = 11.9, 3.5 Hz, 1H), 2.65 (dq, J = 15.7, 3.6 Hz, 1H), 2.44 (td, J = 10.9, 4.3 Hz, 1H), 2.24 (s, 3H), 1.99 (s, 3H), 1.86–1.69 (m, 3H), 1.64–1.55 (m, 3H), 1.54–1.39 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.7, 167.9, 155.5, 148.3, 145.1, 138.6, 131.0, 128.9, 128.9, 126.3, 125.3, 122.3, 121.1, 114.0, 110.5, 101.9, 91.5, 55.4, 40.1, 39.3, 32.0, 26.9, 26.8, 25.3, 23.9, 22.1, 12.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H31N3O5 502.2336; Found 502.2338.
- 7-benzoyl-12-benzyl-2,3,7,12-tetrahydro-1H-6,13a-epoxypyrrolo[2′,1′:2,3][1,3]oxazocino[8,7-b]indol-5(6H)-one (3bq): White solid (yield: 42.2 mg, 91%). M.P. = 114.5–114.8 °C; 1H NMR (400 MHz, CDCl3): δ 7.38–7.29 (m, 6H), 7.22 (t, J = 3.56 Hz, 2H), 7.14 (dd, J = 7.4, 0.7 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H), 7.01 (td, J = 7.7, 1.2 Hz, 1H), 6.89 (td, J = 7.7, 1.2Hz, 1H), 6.47 (d, J = 7.8 Hz, 2H), 5.37 (s, 1H), 5.03 (d, J = 15.1 Hz, 1H), 4.63 (d, J = 15.4 Hz, 1H), 4.59 (s, 1H), 3.83–3.75 (m, 1H), 3.22–3.15 (m, 1H), 2.12–2.03 (m, 1H), 1.89–1.80 (m, 2H), 1.26–1.19 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 195.4, 173.5, 173.5, 142.5, 136.3, 135.5, 133.0, 128.9, 128.9, 128.3, 127.9, 127.6, 127.4, 126.3, 125.4, 123.0, 108.5, 108.4, 81.4, 59.6, 56.6, 44.3, 42.6, 26.3, 25.8 ppm; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H24N2O4 465.1809; Found 465.1761.
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Entry | [M] | Time (h) | Yield [b] (%) | dr [c] |
---|---|---|---|---|
1 | Ru(bpy)3Cl2·6H2O | 10 | trace | − |
2 | Ru(OAc)3 | 10 | 43 | >20:1 |
3 | Rh2(Oct)4 | 10 | 43 | >20:1 |
4 | Pd2(dba)3 | 10 | 66 | >20:1 |
5 | Pd(PPh3)2Cl2 | 10 | 75 | >20:1 |
6 | Rh(OAc)3 | 10 | 70 | >20:1 |
7 | Rh2(OAc)4 | 2.0 | 82 | >20:1 |
8 [d] | Rh2(OAc)4 | 12 | NR [e] | − |
Entry | Ligand | Time (h) | Yield [b] (%) | dr [c] |
---|---|---|---|---|
1 | - | 2.0 | 82 | >20:1 |
2 | dppb | 6.0 | 73 | >20:1 |
3 | dppf | 10 | trace | − |
4 | (±)-L1 | 10 | trace | − |
5 | (±)-L2 | 6.0 | 77 | >20:1 |
6 | (±)-L3 | 1.0 | 88 | >20:1 |
7 | (±)-L4 | 10 | trace | − |
8 | (±)-L5 | 1.0 | 78 | >20:1 |
9 | L6 | 10 | trace | − |
Entry | Solvent | Time (h) | Yield [b] (%) | dr [c] |
---|---|---|---|---|
1 | benzene | 1.0 | 88 | >20:1 |
2 | 1,4-dioxane | 5.0 | 22 | >20:1 |
3 | THF | 5.0 | 35 | >20:1 |
4 | toluene | 0.5 | 73 | >20:1 |
5 | PhCF3 | 1.0 | 80 | >20:1 |
6 | DMF | 10 | NR [d] | − |
7 | HFIP | 10 | trace | − |
8 | 1,2-DCE | 1.0 | 98 | >20:1 |
9 | DCM | 10 | trace | − |
Entry | 1 | 2 (R2, R3, R4) | 3 | Time (h) | Yield [b] (%) | dr [c] |
---|---|---|---|---|---|---|
1 | 1a | 2a (C6H5, C6H5, Me) | 3aa | 1.0 | 98 | >20:1 |
2 | 1a | 2b (4-BrC6H4, C6H5, Me) | 3ab | 0.5 | 73 | >20:1 |
3 | 1a | 2c (4-NO2C6H4, C6H5, Me) | 3ac | 0.5 | 65 | >20:1 |
4 | 1a | 2d (4-MeOC6H4, C6H5, Me) | 3ad | 1.0 | 82 | >20:1 |
5 | 1a | 2e (2-Naphthyl, C6H5, Me) | 3ae | 0.5 | 80 | >20:1 |
6 | 1a | 2f (C6H5, 4-ClC6H4, Me) | 3af | 0.5 | 72 | >20:1 |
7 | 1a | 2g (C6H5, 4-MeC6H4, Me) | 3ag | 1.0 | 80 | >20:1 |
8 | 1a | 2h (C6H5, C6H5, C6H5) | 3ah | 1.0 | 88 | >20:1 |
9 | 1a | 2i (C6H5, Me, C6H5) | 3ai | 24 | NR [d] | − |
10 | 1a | 2j (C6H5, Me, Me) | 3aj | 24 | NR [d] | − |
11 | 1a | 2k (C6H5, Me, H) | 3ak | 24 | NR [d] | − |
12 | 1b | 2a (C6H5, C6H5, Me) | 3ba | 0.1 | 77 | >20:1 |
13 | 1c | 2a (C6H5, C6H5, Me) | 3ca | 0.5 | 70 | >20:1 |
14 | 1d | 2a (C6H5, C6H5, Me) | 3da | 0.5 | 75 | >20:1 |
15 | 1e | 2a (C6H5, C6H5, Me) | 3ea | 0.5 | 82 | >20:1 |
16 | 1f | 2a (C6H5, C6H5, Me) | 3fa | 16 | 35 | >20:1 |
17 | 1g | 2a (C6H5, C6H5, Me) | 3ga | 24 | NR [d] | − |
18 | 1b | 2b (4-BrC6H4, C6H5, Me) | 3bb | 0.1 | 90 | >20:1 |
19 | 1b | 2c (4-NO2C6H4, C6H5, Me) | 3bc | 0.1 | 80 | >20:1 |
20 | 1b | 2l (3,4,5-tri-MeOC6H2, C6H5, Me) | 3bl | 0.1 | 77 | >20:1 |
21 | 1b | 2m (4-CF3C6H4, C6H5, Me) | 3bm | 0.1 | 88 | >20:1 |
22 | 1b | 2n (2-MeOC6H4, C6H5, Me) | 3bn | 0.1 | 93 | >20:1 |
23 | 1b | 2o | 3bo | 0.1 | 95 | >20:1 |
24 | 1c | 2c (4-NO2C6H4, C6H5, Me) | 3cc | 0.3 | 80 | >20:1 |
25 | 1c | 2d (4-MeOC6H4, C6H5, Me) | 3cd | 0.3 | 90 | >20:1 |
26 | 1c | 2e (2-Naphthyl, C6H5, Me) | 3ce | 1.0 | 95 | >20:1 |
27 | 1c | 2f (C6H5, 4-ClC6H4, Me) | 3cf | 1.0 | 80 | >20:1 |
28 | 1c | 2g (C6H5, 4-MeC6H4, Me) | 3cg | 1.0 | 84 | >20:1 |
29 | 1c | 2l (3,4,5-tri-MeOC6H2, C6H5, Me) | 3cl | 1.0 | 75 | >20:1 |
30 | 1c | 2n (2-MeOC6H4, C6H5, Me) | 3cn | 1.0 | 86 | >20:1 |
31 | 1c | 2p (2-Thienyl, C6H5, Me) | 3cp | 1.0 | 85 | >20:1 |
32 | 1d | 2b (4-BrC6H4, C6H5, Me) | 3db | 1.0 | 60 | >20:1 |
33 | 1d | 2d (4-MeOC6H4, C6H5, Me) | 3dd | 1.0 | 78 | >20:1 |
34 | 1d | 2e (2-Naphthyl, C6H5, Me) | 3de | 1.0 | 91 | >20:1 |
35 | 1d | 2g (C6H5, 4-MeC6H4, Me) | 3dg | 1.0 | 90 | >20:1 |
36 | 1d | 2l (3,4,5-tri-MeOC6H2, C6H5, Me) | 3dl | 1.0 | 82 | >20:1 |
37 | 1d | 2n (2-MeOC6H4, C6H5, Me) | 3dn | 1.0 | 81 | >20:1 |
38 | 1e | 2d (4-MeOC6H4, C6H5, Me) | 3ed | 1.0 | 85 | >20:1 |
39 | 1e | 2l (3,4,5-tri-MeOC6H2, C6H5, Me) | 3el | 1.0 | 90 | >20:1 |
40 | 1e | 2n (2-MeOC6H4, C6H5, Me) | 3en | 1.0 | 50 | >20:1 |
41 | 1b | 2q | 3bq | 1.0 | 91 | >20:1 |
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Wang, K.; Zhang, Y.; Cai, L.-Y.; Song, X.-Q.; Wang, C.; Zhang, J.-R.; Pan, Y.-F.; Zhao, H.-W. Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines. Molecules 2023, 28, 7021. https://doi.org/10.3390/molecules28207021
Wang K, Zhang Y, Cai L-Y, Song X-Q, Wang C, Zhang J-R, Pan Y-F, Zhao H-W. Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines. Molecules. 2023; 28(20):7021. https://doi.org/10.3390/molecules28207021
Chicago/Turabian StyleWang, Kuo, Yue Zhang, Lu-Yu Cai, Xiu-Qing Song, Chen Wang, Jia-Rui Zhang, Yi-Fan Pan, and Hong-Wu Zhao. 2023. "Diastereoselective Cascade Cyclization of Diazoimides with Alkylidene Pyrazolones for Preparation of Pyrazole-Fused Oxa-Bridged Oxazocines" Molecules 28, no. 20: 7021. https://doi.org/10.3390/molecules28207021