Potassium Carbonate → Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl ester

HRID 1424852노트

반응식

HRID 1424852 반응식
F[C:2]1[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH:15]1([C:18]2[C:19]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:20][C:21]3[O:25][C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[C:23]([C:33]([NH:35][CH3:36])=[O:34])[C:22]=3[CH:37]=2)[CH2:17][CH2:16]1.C([O-])([O-])=O.[K+].[K+]>CN(C)P(N(C)C)(N(C)C)=O.CCOC(C)=O>[CH:15]1([C:18]2[C:19]([N:38]([C:2]3[CH:3]=[CH:4][C:5]([N+:12]([O-:14])=[O:13])=[C:6]([CH:11]=3)[C:7]([O:9][CH3:10])=[O:8])[S:39]([CH3:42])(=[O:41])=[O:40])=[CH:20][C:21]3[O:25][C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[C:23]([C:33](=[O:34])[NH:35][CH3:36])[C:22]=3[CH:37]=2)[CH2:17][CH2:16]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 51520495-Fluoro-2-nitrobenzoic acid methyl esterHCID 160735125-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

생성물 1

HCID 122643071Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl ester수율 55.4%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 12679Hexamethylphosphoramide용매

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온도
60 °C

실험 절차

A mixture of methyl 5-fluoro-2-nitrobenzoate (2.138 g, 10.73 mmol), 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (4.0 g, 9.94 mmol) and K2CO3 (4.12 g, 29.8 mmol) in hexamethylphosphoramide (25 mL) in a seal tube was stirred at 60° C. for 3 days. Cooled down to room temperature, the mixture was diluted with EtOAc and then filtered through a pad of Celite. The filtrate was washed with water and brine and dried over Na2SO4. Concentrated under reduced pressure, the residue was purified by flashing chromatography on silica gel eluted with 0-50% EtOAc in hexane to give the product (3.2 g, 55%) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.00 (d, J=9.17 Hz, 1H) 7.89 (dd, J=8.78, 5.27 Hz, 2H) 7.55 (d, J=9.37 Hz, 2H) 7.50 (dd, J=9.07, 2.63 Hz, 1H) 7.44 (d, J=2.73 Hz, 1H) 7.23 (t, J=8.68 Hz, 2H) 5.81 (d, J=4.49 Hz, 1H) 3.91 (s, 3H) 3.35 (s, 3H) 3.02 (d, J=4.88 Hz, 3H) 1.86-1.96 (m, 1H) 0.97-1.05 (m, 1H) 0.89 (br. s., 2H) 0.59 (br. s., 1H). LCMS (m/z, ES+)=582 (M+H+).

후처리

  1. temperatureCooled down to room temperature
  2. filtrationfiltered through a pad of Celite
  3. washThe filtrate was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentrated under reduced pressure
  6. customthe residue was purified
  7. washeluted with 0-50% EtOAc in hexane

출처 및 근거

ORD 기록
ord-5d02c982bacd442f9cced53537e1ab57
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927593B2

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