Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Materials and Instrumentation
3.2. Syntheses
3.2.1. Synthesis of P3
3.2.2. Synthesis of P4
3.2.3. Synthesis of P6
3.2.4. Synthesis of 1
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Entry | Base | Temperature | Yield |
---|---|---|---|
1 | TEA (1.2 equiv) | −5 °C | 56% |
2 | Pyridine (1.2 equiv) | −5 °C | 95% |
3 | Pyridine (1.2 equiv) | −10 °C | 90% |
4 | Pyridine (1.2 equiv) | 8 °C | 79% |
5 | NaOCH3 (1.2 equiv) | −5 °C | 36% |
6 | Mg(OCH3)2 (0.6 equiv) | −5 °C | 85% |
Entry | Base | Additive | Yield a | |
---|---|---|---|---|
P6 | P6-Isos | |||
1 | TEA (0.5 equiv) | \ | 10% | 25% |
2 | DIPEA (1.0 equiv) | \ | 20% | 25% |
3 | sodium tert-butoxide (1.0 equiv) | \ | 2% | 2% |
4 | DIPEA (1.0 equiv) | MgBr2 | 50% | 10% |
5 | DIPEA (1.0 equiv) | MgCl2 | 38% | 15% |
6 | DIPEA (1.0 equiv) | MgI2 | 51% | 10% |
7 | DIPEA (1.0 equiv) | MgSO4 | 23% | 20% |
8 | Mg(OCH3)2 (0.5 equiv) | \ | 10% | 10% |
Entry | Base | Temperature | Yield | |
---|---|---|---|---|
1 | 1-a | |||
1 | NaOH (2.0 equiv) | 0 °C | 62% | 32% |
2 | KOH (2.0 equiv) | 0 °C | 59% | 35% |
3 | LiOH (2.0 equiv) | 0 °C | 90% | 8% |
4 * | LiOH (2.0 equiv) | −10 °C | 91% | 7% |
5 | LiOH (2.0 equiv) | 10 °C | 82% | 15% |
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Kong, J.; Xia, H.; He, R.; Chen, H.; Yu, Y. Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization. Molecules 2021, 26, 2850. https://doi.org/10.3390/molecules26102850
Kong J, Xia H, He R, Chen H, Yu Y. Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization. Molecules. 2021; 26(10):2850. https://doi.org/10.3390/molecules26102850
Chicago/Turabian StyleKong, Jiahui, Haijian Xia, Renbao He, Hao Chen, and Yongping Yu. 2021. "Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization" Molecules 26, no. 10: 2850. https://doi.org/10.3390/molecules26102850
APA StyleKong, J., Xia, H., He, R., Chen, H., & Yu, Y. (2021). Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization. Molecules, 26(10), 2850. https://doi.org/10.3390/molecules26102850