The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Synthesis of 4-Amino-2-(methylthio)-N-phenylthiazole-5-carboxamide (7a)
3.2. Synthesis of 2-(Methylthio)-6-phenylthiazolo [4,5-d]pyrimidin-7(6H)-one (8aa)
3.3. Synthesis of 2-(Methylsulfonyl)-6-phenylthiazolo [4,5-d]pyrimidin-7(6H)-one (9aa)
3.4. Synthesis of 2-(Butylamino)-6-phenylthiazolo [4,5-d]pyrimidin-7(6H)-One (1aaa)
3.5. Preparation of 4-Amino-N-(substituted)thiazole-5-carboxamide resin (12a) (R1 = Ph)
3.6. Prepared of 2-(Methylthio)-6-phenylthiazolo [4,5-d]pyrimidin-7(6H)-one resin (13aa)
3.7. Prepared of 2-(Methylsulfonyl)-6-phenylthiazolo[4,5-d]pyrimidin-7(6H)-one resin (14aa)
3.8. Synthesis of 2-(Butylamino)-6-phenylthiazolo[4,5-d]pyrimidin-7(6H)-one (1aaa)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Entry a | Base | Solvent | Temp (°C) | Yield (%) b |
---|---|---|---|---|
1 | 1 M NaOH | Acetone/H2O | 60 | 57 |
2 | KOH | Acetone/H2O | 60 | 41 |
3 | LiOH | Acetone/H2O | 60 | 98 |
4 | NaOEt | EtOH | Reflux | 16 |
5 | K2CO3 | Acetone/H2O | 60 | N.R d |
6 | NaH | THF | R.T c | N.R d |
7 | Et3N | Acetone/H2O | 60 | N.R d |
8 | DBU | Acetone/H2O | 60 | 21 |
Entry a | Catalyst (mol%) | R2 Reagent | Solvent | Temp (°C) | Time (h) | Yield (%) b |
---|---|---|---|---|---|---|
1 | HC(OEt)3 | Ac2O | 100 | 10 | NR c | |
2 | p-TsOH(10) | HC(OEt)3 | Toluene | 120 | 23 | 14 |
3 | p-TsOH(10) | HC(OEt)3 | EtOH | Reflux | 2 | 70 |
4 | p-TsOH(10) | HC(OEt)3 | DMF | 120 | 10 | 64 |
5 | HC(OEt)3 | AcOH | Reflux | 48 | 43 | |
6 | p-TsOH(10) | HC(OEt)3 | THF | Reflux | 24 | NR c |
7 | AlCl3(10) | HC(OEt)3 | EtOH | Reflux | 10 | Trace |
8 | BF3OEt2(10) | HC(OEt)3 | EtOH | Reflux | 5 | 64 |
9 | CSA(10) | HC(OEt)3 | EtOH | 60 | 3 | 79 |
10 | CSA(10) | MeC(OEt)3 | EtOH | 60 | 10 | 75 |
11 | I2(120) | Benzaldehyde | DMSO | 100 | 0.5 | 80 |
Entry a | R1 | R2 | R3 | Yield b (%) | Entry a | R1 | R2 | R3 | Yield b (%) |
---|---|---|---|---|---|---|---|---|---|
1 | Ph | H | a | 81 | 30 | 4-OMe-Ph | Me | b | 74 |
2 | Ph | H | b | 77 | 31 | 4-OMe-Ph | Me | c | 77 |
3 | Ph | H | c | 70 | 32 | 4-OMe-Ph | Me | d | 88 |
4 | Ph | H | e | 65 | 33 | 4-OMe-Ph | Me | e | 83 |
5 | Ph | H | f | 36 | 34 | 4-OMe-Ph | Me | f | 33 |
6 | Ph | H | g | 67 | 35 | 4-OMe-Ph | Me | g | 73 |
7 | Ph | H | h | 77 | 36 | 4-OMe-Ph | Me | h | 93 |
8 | Ph | H | i | 82 | 37 | 4-OMe-Ph | Me | i | 85 |
9 | Ph | H | j | 90 | 38 | 4-OMe-Ph | Me | j | 86 |
10 | Ph | Me | a | 85 | 39 | 4-Me-Ph | Me | a | 40 |
11 | Ph | Me | b | 77 | 40 | 4-Me-Ph | Me | b | 47 |
12 | Ph | Me | c | 82 | 41 | 4-Me-Ph | Me | c | 51 |
13 | Ph | Me | d | 76 | 42 | 4-Me-Ph | Me | e | 46 |
14 | Ph | Me | e | 79 | 43 | 4-Me-Ph | Me | g | 48 |
15 | Ph | Me | f | 37 | 44 | 4-Me-Ph | Me | h | 49 |
16 | Ph | Me | g | 75 | 45 | 4-Me-Ph | Me | j | 64 |
17 | Ph | Me | h | 91 | 46 | 4-NO2-Ph | H | a | 52 |
18 | Ph | Me | i | 88 | 47 | 4-NO2-Ph | H | c | 39 |
19 | Ph | Me | j | 92 | 48 | 4-NO2-Ph | H | e | 55 |
20 | 4-OMe-Ph | H | a | 68 | 49 | 4-NO2-Ph | H | f | 49 |
21 | 4-OMe-Ph | H | b | 86 | 50 | 4-NO2-Ph | H | h | 65 |
22 | 4-OMe-Ph | H | c | 77 | 51 | 4-NO2-Ph | H | i | 53 |
23 | 4-OMe-Ph | H | d | 76 | 52 | 4-NO2-Ph | H | j | 53 |
24 | 4-OMe-Ph | H | e | 63 | 53 | 4-NO2-Ph | Me | a | 48 |
25 | 4-OMe-Ph | H | g | 68 | 54 | 4-NO2-Ph | Me | b | 18 |
26 | 4-OMe-Ph | H | h | 80 | 55 | 4-NO2-Ph | Me | d | 47 |
27 | 4-OMe-Ph | H | i | 75 | 56 | 4-NO2-Ph | Me | e | 53 |
28 | 4-OMe-Ph | H | j | 79 | 57 | 4-NO2-Ph | Me | j | 57 |
29 | 4-OMe-Ph | Me | a | 72 |
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Hua, S.; Moon, J.; Lee, T. The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives. Molecules 2025, 30, 430. https://doi.org/10.3390/molecules30020430
Hua S, Moon J, Lee T. The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives. Molecules. 2025; 30(2):430. https://doi.org/10.3390/molecules30020430
Chicago/Turabian StyleHua, Shuanghui, Jimin Moon, and Taeho Lee. 2025. "The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives" Molecules 30, no. 2: 430. https://doi.org/10.3390/molecules30020430
APA StyleHua, S., Moon, J., & Lee, T. (2025). The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives. Molecules, 30(2), 430. https://doi.org/10.3390/molecules30020430