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【结 构 式】

【分子编号】29602

【品名】2-[5-methoxy-2-nitro-4-(trifluoromethyl)phenyl]acetonitrile

【CA登记号】

【 分 子 式 】C10H7F3N2O3

【 分 子 量 】260.1724696

【元素组成】C 46.17% H 2.71% F 21.91% N 10.77% O 18.45%

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:(III)

Reaction between 1-methoxy-4-nitro-2-trifluoromethylbenzene (I) and 4-chlorophenoxyacetonitrile (II) in the presence of potassium tert-butoxide produced aryl acetonitrile (III). Catalytic hydrogenation of (III) gave rise to indole (IV), which was further reduced to indoline (V) employing sodium cyanoborohydride and AcOH.

1 Gaster, L.M.; Wyman, P.A.; Mulholland, K.R.; Davies, D.T.; Duckworth, D.M.; Forbes, I.T.; Jones, G.E. (SmithKline Beecham plc); Indole derivs. as 5-HT receptor antagonist. EP 0808312; JP 1998513442; US 5990133; WO 9623783 .
2 Blackburn, T.P. (SmithKline Beecham plc); Pharmaceutical compsn. containing a 5HT2C antagonist and a D2 antagonist. WO 9804289 .
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) 29600 methyl 4-nitro-2-(trifluoromethyl)phenyl ether; 1-methoxy-4-nitro-2-(trifluoromethyl)benzene 654-76-2 C8H6F3NO3 详情 详情
(II) 29601 2-(4-chlorophenoxy)acetonitrile 3598-13-8 C8H6ClNO 详情 详情
(III) 29602 2-[5-methoxy-2-nitro-4-(trifluoromethyl)phenyl]acetonitrile C10H7F3N2O3 详情 详情
(IV) 29603 methyl 6-(trifluoromethyl)-1H-indol-5-yl ether; 5-methoxy-6-(trifluoromethyl)-1H-indole C10H8F3NO 详情 详情
(V) 29604 methyl 6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl ether; 5-methoxy-6-(trifluoromethyl)indoline C10H10F3NO 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

Treatment of 1-methoxy-4-nitro-2-(trifluoromethyl)benzene (I) with 4-chlorophenoxyacetonitrile (II) in the presence of potassium tert-butoxide afforded the arylacetonitrile (III). Reductive cyclization of (III) upon treatment with H2 and Pd/C produced indole (IV), which was further reduced to indoline (V) with NaBH3CN and AcOH. Methyl ether cleavage in (V) using ISiMe3 yielded phenol (VI). After protection of the amino group of (VI) as the acetamide (VII), sulfonylation at the phenol group with trifluoromethanesulfonic anhydride and pyridine gave triflate (VIII). The triflate group was then displaced with tetramethyltin in the presence of palladium catalyst to furnish, after hydrolysis of the acetamide, the 5-methyl-6-(trifluoromethyl)indoline (IX).

1 Blackburn, T.P. (SmithKline Beecham plc); Pharmaceutical compsn. containing a 5HT2C antagonist and a D2 antagonist. WO 9804289 .
2 Bromidge, S.M.; Forbes, I.T. (SmithKline Beecham plc); Indoline derivs. useful as 5-HT-2C receptor antagonists. EP 0912554; WO 9748699 .
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) 29600 methyl 4-nitro-2-(trifluoromethyl)phenyl ether; 1-methoxy-4-nitro-2-(trifluoromethyl)benzene 654-76-2 C8H6F3NO3 详情 详情
(II) 29601 2-(4-chlorophenoxy)acetonitrile 3598-13-8 C8H6ClNO 详情 详情
(III) 29602 2-[5-methoxy-2-nitro-4-(trifluoromethyl)phenyl]acetonitrile C10H7F3N2O3 详情 详情
(IV) 29603 methyl 6-(trifluoromethyl)-1H-indol-5-yl ether; 5-methoxy-6-(trifluoromethyl)-1H-indole C10H8F3NO 详情 详情
(V) 29604 methyl 6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl ether; 5-methoxy-6-(trifluoromethyl)indoline C10H10F3NO 详情 详情
(VI) 29605 6-(trifluoromethyl)-5-indolinol C9H8F3NO 详情 详情
(VII) 29606 1-[5-hydroxy-6-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]-1-ethanone C11H10F3NO2 详情 详情
(VIII) 29607 1-acetyl-6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-yl trifluoromethanesulfonate C12H9F6NO4S 详情 详情
(IX) 29608 5-methyl-6-(trifluoromethyl)indoline C10H10F3N 详情 详情
Extended Information