Water → ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate

HRID 1424874노트

반응식

HRID 1424874 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:22]3[C:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)[O:25][C:21]=3[CH:20]=2)[CH:15]=[CH:16][CH:17]=1.[CH3:43][S:44](Cl)(=[O:46])=[O:45].O>C1COCC1.CCOC(C)=O>[Br:11][C:12]1[CH:13]=[C:14]([N:18]([C:19]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:22]3[C:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:24]([C:26]4[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=4)[O:25][C:21]=3[CH:20]=2)[S:44]([CH3:43])(=[O:46])=[O:45])[CH:15]=[CH:16][CH:17]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 71258359Ethyl 6-((3-bromophenyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate

생성물 1

HCID 131732322ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate수율 37.5%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

A solution of lithium bis(trimethylsilyl)amide (1M in THF) (1.93 mL, 1.93 mmol) was added dropwise to a solution of ethyl 6-((3-bromophenyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate (734 mg, 1.48 mmol) in THF (10 mL) at −78° C. The mixture was stirred for 45 minutes and then a solution of methanesulfonyl chloride (0.463 mL, 5.94 mmol) in THF (1.5 mL) was added at −78° C. After complete addition the reaction mixture was allowed to warm to room temperature overnight. Water and EtOAc were added. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (hexane:EtOAc) to give ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate (318 mg, 37%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1H) 8.03-8.13 (m, 2H) 7.62-7.66 (m, 1H) 7.59 (s, 1H) 7.43 (s, 4H) 7.30-7.39 (m, 1H) 4.26-4.41 (m, 2H) 3.42 (s, 3H) 2.12-2.26 (m, 1H) 1.28-1.37 (m, 3H) 0.71-1.14 (m, 4H) 0.41 (m, 1H). %). LCMS (m/z, ES+)=572, 574 (M+H, M+2).

후처리

  1. additionAfter complete addition the reaction mixture
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (hexane:EtOAc)

출처 및 근거

ORD 기록
ord-82a436d764f84062b5704b1a97eb6386
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927593B2

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