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【结 构 式】

【分子编号】16610

【品名】(2-isopropyl-1,3-thiazol-4-yl)-N-methylmethanamine; N-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-N-methylamine

【CA登记号】154212-60-9

【 分 子 式 】C8H14N2S

【 分 子 量 】170.27864

【元素组成】C 56.43% H 8.29% N 16.45% S 18.83%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXVI)

The N-substituted valine (XIII) has been synthesized as follows: The reaction of isobutyramide (XXII) with phosphorus pentasulfide (P4S10) in ethyl ether gives the corresponding thioamide (XXIII), which is cyclized with 1,3-dichloroacetone (XXIV) by means of MgSO4 in refluxing acetone yielding 4-(chloromethyl)-2-isopropylthiazole (XXV). The reaction of (XXV) with methylamine in water affords N-(2-isopropylthiazol-4-ylmethyl)-N-methylamine (XXVI), which is condensed with N-(4-nitrophenoxycarbonyl)-L-valine methyl ester (XXVII) by means of 4-(dimethylamino)pyridine (DMAP) and triethylamine in refluxing THF to give the thiazol-substituted L-valine ester (XXVIII). Finally, this compound is converted into the corresponding free acid with LiOH in dioxane/water. The N-(4-nitrophenoxycarbonyl)-L-valine methyl ester (XXVII) has been synthesized by reaction of chloroformate (XXI) with L-valine methyl ester (XXIX) by means of 4-methylmorpholine (MPH) in dichloromethane.

1 Graul, A.; Castañer, J.; Ritonavir. Drugs Fut 1996, 21, 7, 700.
2 Kempf, D.J.; Norbeck, D.W.; Sham, H.L.; Zhao, C.; Sowin, T.J.; Reno, D.S.; Haight, A.R.; Cooper, A.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds. EP 0674513; EP 0727419; JP 1996505844; JP 1997118679; JP 1998087639; WO 9414436 .
3 Al-Razzak, L.; Marsh, K.C.; Manning, L.P.; Kaul, D. (Abbott Laboratories Inc.); Pharmaceutical compsns. containing HIV protease inhibitors. EP 0732923; US 5484801; WO 9520384 .
4 Flentge, C.; Kempf, D.; Marsh, K.; et al.; Symmetry-based inhibitors of HIV protease with high oral bioavailability. 207th ACS Natl Meet (March 13-17, San Diego) 1994, Abst MEDI 35.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIII) 16597 (2S)-2-([[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl]amino)-3-methylbutyric acid C14H23N3O3S 详情 详情
(XXI) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(XXII) 16606 Isobutyramide; 2-methylpropanamide 563-83-7 C4H9NO 详情 详情
(XXIII) 16607 2-methylpropanethioamide 13515-65-6 C4H9NS 详情 详情
(XXIV) 63907 1,3-dichloroacetone C3H4Cl2O 详情 详情
(XXV) 16609 4-(chloromethyl)-2-isopropyl-1,3-thiazole C7H10ClNS 详情 详情
(XXVI) 16610 (2-isopropyl-1,3-thiazol-4-yl)-N-methylmethanamine; N-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-N-methylamine 154212-60-9 C8H14N2S 详情 详情
(XXVII) 16611 methyl (2S)-3-methyl-2-[[(4-nitrophenoxy)carbonyl]amino]butanoate C13H16N2O6 详情 详情
(XXVIII) 16612 methyl (2S)-2-([[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl]amino)-3-methylbutanoate C15H25N3O3S 详情 详情
(XXIX) 16613 methyl (2S)-2-amino-3-methylbutanoate C6H13NO2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XLI)

中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
Extended Information