• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】68086

【品名】(R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-methoxy-5-oxopentanoic acidN-Fmoc-L-glutamic acid 5-methyl ester

【CA登记号】 

【 分 子 式 】C21H21NO6

【 分 子 量 】383.40088

【元素组成】C 65.79% H 5.52% N 3.65% O 25.04%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

Condensation of 5-bromoanthranilic acid (I) with the lithium derivative of 2-bromopyridine (II) in cold THF/ethyl ether gives the diaryl ketone (III). N-Fmoc-L-glutamic acid 5-methyl ester (IV) is chlorinated with oxalyl chloride and catalytic DMF to produce the acid chloride (V), which is then coupled with the amino ketone (III) in boiling chloroform to afford amide (VI). Base-mediated deprotection of amine (VI), followed by cyclization by treatment with AcOH in dichloroethane leads to the benzodiazepinone (VII). Subsequent treatment of lactam (VII) with bis-morpholinophosphorochloridate and NaH affords the imino phosphate (VIII), which is then condensed with 1-amino-2-propanol (IX) producing amidine (X). Finally, remimazolam is obtained by Swern oxidation of the secondary alcohol of (X), followed by cyclization under acidic conditions .

1 Jung, D.K., Pacofsky, G.J., Stafford, J.A., Feldman, P.L., Kaldor, I., Tidwell, J.H. (GlaxoSmithKline plc). Short-acting benzodiazepines. EP 1183243, JP 2002544266, JP 2006151984, JP 2007197468, JP 2007197469, US 7160880, US 2007093475,US 2007135419, US 2007135420, US 2007135421, US 7435730, US 7528127, US 7473689, US 7485635, WO 2000069836
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 31634 2-amino-5-bromobenzoic acid 5794-88-7 C7H6BrNO2 详情 详情
(II) 29052 2-Bromopyridine;α-bromopyridine;α-bromoazine 109-04-6 C5H4BrN 详情 详情
(III) 68085 (2-amino-5-bromophenyl)(pyridin-2-yl)methanone 1563-56-0 C12H9BrN2O 详情 详情
(IV) 68086 (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-methoxy-5-oxopentanoic acidN-Fmoc-L-glutamic acid 5-methyl ester   C21H21NO6 详情 详情
(V) 68087 (R)-methyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-chloro-5-oxopentanoate   C21H20ClNO5 详情 详情
(VI) 68088 (S)-methyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-((4-bromo-2-picolinoylphenyl)amino)-5-oxopentanoate   C33H28BrN3O6 详情 详情
(VII) 68089 (S)-methyl 3-(7-bromo-2-oxo-5-(pyridin-2-yl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanoate   C18H16BrN3O3 详情 详情
(VIII) 68090 (S)-methyl 3-(7-bromo-2-((dimorpholinophosphoryl)oxy)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepin-3-yl)propanoate   C26H31BrN5O6P 详情 详情
(IX) 41397 1-amino-2-propanol 78-96-6 C3H9NO 详情 详情
(X) 68091 methyl 3-((3S)-7-bromo-2-((2-hydroxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepin-3-yl)propanoate   C21H23BrN4O3 详情 详情
Extended Information