【结 构 式】 |
【分子编号】41488 【品名】methyl 6-chloro-4-iodo-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C10H7ClINO2 【 分 子 量 】335.52829 【元素组成】C 35.8% H 2.1% Cl 10.57% I 37.82% N 4.17% O 9.54% |
合成路线1
该中间体在本合成路线中的序号:(IV)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 |