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【结 构 式】 
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【分子编号】67624 【品名】lithium potassium 3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)pyrrolo[2,3-c]pyridin-1-ide bromide 【CA登记号】 |
【 分 子 式 】C24H22LiN7O4.KBr 【 分 子 量 】598.427 【元素组成】C 48.17% H 3.70% Br 13.35% K 6.53% Li 1.16% N 16.38% O 10.69% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)Condensation of compound (XXIX) or its free base with 1-benzoylpiperazine hydrochloride (IX) in the presence of CDI in DMF at 10 °C yields the corresponding carboxamide (XXX), which by Ullmann-Goldberg-Buchwald reaction with 3-methyl-1,2,4-triazole (III) using CuI, t-DAMCH and KOH in acetonitrile/H2O followed by addition of LiBr affords the lithium salt of azaindole (X), isolated as KBr co-crystal (XXXI). Finally, selective N-alkylation of compound (XXXI) with di-tert-butyl chloromethyl phosphate (XI) in the presence of K3PO4 and Et4NI or K2CO3 in acetonitrile/CH2Cl2 results in the phosphate ester (XIV) , which is finally hydrolyzed using AcOH in water .
| 【1】 Chen, K., Risatti, C., Bultman, M. et al. Synthesis of the 6-azaindole containing HIV-1 attachment inhibitor pro-drug, BMS-663068. J Org Chem 2014, 79(18): 8757-67. |
| 【2】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038709. |
| 【3】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038710. |
| 【4】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038711. |
| 【5】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038712. |
| 【6】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038716. |
| 【7】 Eastgate, M.D., Bultman, M.S., Chen, K. et al. (Bristol-Myers Squibb Co.). Methods for the preparation of HIV attachment inhibitor piperazine prodrug compound. US 2015038717. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 42239 | di(tert-butyl) chloromethyl phosphate;di-tert-butyl chloromethyl phosphate；PHOSPHORIC ACI DI-T-BUTYL EXTER CHLOROMETHYL ESTER | 229625-50-7 | C9H20ClO4P | 详情 | 详情 |
| (III) | 67601 | 3-methyl-1,2,4-triazole；3-Methyltriazole；3-Methyl-1H-1,2,4-triazole；3-Methyl-4H-1,2,4-triazole | 7170-01-6 | C3H5N3 | 详情 | 详情 |
| (IX) | 67606 | 1-benzoylpiperazine;4-Benzoylpiperazine;N-Benzoylpiperazine;(Phenyl)(piperazin-1-yl)methanone | 13754-38-6 | C11H14N2O | 详情 | 详情 |
| (XIV) | 67609 | (3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl)methyl di-tert-butyl phosphate | C33H42N7O8P | 详情 | 详情 | |
| (XXIX) | 67622 | 2-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid hydrobromide | C10H7BrN2O4.HBr | 详情 | 详情 | |
| (XXX) | 67623 | 1-(4-benzoylpiperazin-1-yl)-2-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione | C21H19BrN4O4 | 详情 | 详情 | |
| (XXXI) | 67624 | lithium potassium 3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)pyrrolo[2,3-c]pyridin-1-ide bromide | C24H22LiN7O4.KBr | 详情 | 详情 |