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【结 构 式】

【分子编号】41491

【品名】methyl 6-chloro-4-[(Z)-5-ethoxy-5-oxo-3-pentenyl]-1H-indole-2-carboxylate

【CA登记号】n/a

【 分 子 式 】C17H18ClNO4

【 分 子 量 】335.78696

【元素组成】C 60.81% H 5.4% Cl 10.56% N 4.17% O 19.06%

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:(VIIb)

Synthesis of intermediate (3S)-(XI): Iodination of 4-chloro-2-nitrotoluene (I) with NaI, I2 and H2SO4 yields (II), which is then treated with dimethyl oxalate (A) in toluene in presence of KOMe or alternatively NaOMe, in MeOH to afford (III). Cyclization of (III) is performed by a first treatment with SnCl2 in dimethoxyethane followed by TiCl3/H2O to provide indole (IV), which is converted into (VI) by reaction with alcohol (V) in presence of NaHCO3, benzyltriethyl ammonium chloride and Pd(OAc)2, followed by a treatment with sodium thiosulfate. The reaction of aldehyde (VI) with KOtBu and triethyl phosphonoacetate (B) in THF yields ethyl ester (VIIa-b), which is then converted into iodo derivative (VIIIa-b) by means of NaI and NCS in DMF. Cyclization of (VIIIa-b) by treatment with Pd(PPh3)4 in DMF and Ag3PO4/H2O affords tetrahydrobenzindole (IX), which is reduced by means of Sm, and I2 in MeOH/THF to give (X). Alternatively (X) is obtained by simultaneous cyclization and reduction of (VIIIa-b) by treatment with SnBu3H and AIBN in chlorobenzene. Finally ethyl ester (X) is selectively hydrolyzed with HCl in HOAc to provide (XI) in its racemic form. Enantiomer (3S)-(XI) can be isolated by separation of the corresponding diasteromers obtained by reaction of (XI) with L-(-) norphedrine in isopropanol followed by hydrolysis with HCl in EtOAc and THF.

1 Katayama, S.; Kishimoto, H.; Ae, N.; Nagata, R. (Sumitomo Pharmaceuticals Co., Ltd.); Tricyclic indole-2-carboxylic acid cpd. used as NMDA receptor antagonist. WO 0056711 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 10019 Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate 867-13-0 C8H17O5P 详情 详情
(A) 37412 methyl 2-methoxy-2-oxoacetate;dimethyl oxalate;Methyl oxalate 553-90-2 C4H6O4 详情 详情
(VIIa) 41490 methyl 6-chloro-4-[(E)-5-ethoxy-5-oxo-3-pentenyl]-1H-indole-2-carboxylate C17H18ClNO4 详情 详情
(VIIb) 41491 methyl 6-chloro-4-[(Z)-5-ethoxy-5-oxo-3-pentenyl]-1H-indole-2-carboxylate n/a C17H18ClNO4 详情 详情
(VIIIa) 41492 methyl 6-chloro-4-[(E)-5-ethoxy-5-oxo-3-pentenyl]-3-iodo-1H-indole-2-carboxylate n/a C17H17ClINO4 详情 详情
(VIIIb) 41493 methyl 6-chloro-4-[(Z)-5-ethoxy-5-oxo-3-pentenyl]-3-iodo-1H-indole-2-carboxylate n/a C17H17ClINO4 详情 详情
(3S)-(XI) 41497 2-[(3S)-7-chloro-2-(methoxycarbonyl)-1,3,4,5-tetrahydrobenzo[cd]indol-3-yl]acetic acid C15H14ClNO4 详情 详情
(I) 41485 4-chloro-1-methyl-2-nitrobenzene;4-chloro-2-nitrotoluene;4-chloro-1-methyl-2-nitro-benzene 89-59-8 C7H6ClNO2 详情 详情
(II) 41486 5-chloro-1-iodo-2-methyl-3-nitrobenzene n/a C7H5ClINO2 详情 详情
(III) 41487 methyl 3-(4-chloro-2-iodo-6-nitrophenyl)-2-oxopropanoate C10H7ClINO5 详情 详情
(IV) 41488 methyl 6-chloro-4-iodo-1H-indole-2-carboxylate C10H7ClINO2 详情 详情
(V) 12234 2-Propen-1-ol; Allyl alcohol 107-18-6 C3H6O 详情 详情
(VI) 41489 methyl 6-chloro-4-(3-oxopropyl)-1H-indole-2-carboxylate C13H12ClNO3 详情 详情
(IX) 41494 methyl 7-chloro-3-[(Z)-2-ethoxy-2-oxoethylidene]-4,5-dihydrobenzo[cd]indole-2(1H)-carboxylate C17H16ClNO4 详情 详情
(X) 41495 methyl 7-chloro-3-(2-ethoxy-2-oxoethyl)-1,3,4,5-tetrahydrobenzo[cd]indole-2-carboxylate C17H18ClNO4 详情 详情
(XI) 41496 2-[7-chloro-2-(methoxycarbonyl)-1,3,4,5-tetrahydrobenzo[cd]indol-3-yl]acetic acid C15H14ClNO4 详情 详情
Extended Information