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Bromine → (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

HRID 1028027
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HRID 1028027 반응식
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([O:13][CH:14]([F:16])[F:15])=[C:9]([F:12])[CH:10]=2)[N:5]([CH:17]2[CH2:20][CH2:19][CH2:18]2)[C:4]=1[C:21]1[N:26]=[CH:25][C:24]([S:27]([NH:30][C@@H:31]([CH3:36])[C:32]([F:35])([F:34])[F:33])(=[O:29])=[O:28])=[CH:23][CH:22]=1)#[N:2].[Br:37]Br.OS([O-])=O.[Na+]>[Fe].ClCCCl>[Br:37][C:10]1[C:9]([F:12])=[C:8]([O:13][CH:14]([F:15])[F:16])[CH:7]=[C:6]2[C:11]=1[C:3]([C:1]#[N:2])=[C:4]([C:21]1[N:26]=[CH:25][C:24]([S:27]([NH:30][C@@H:31]([CH3:36])[C:32]([F:34])([F:35])[F:33])(=[O:28])=[O:29])=[CH:23][CH:22]=1)[N:5]2[CH:17]1[CH2:18][CH2:19][CH2:20]1
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참가 물질

6

반응물 3

HCID 24408BromineHCID 23665763Sodium BisulfiteHCID 71607028(S)-6-(3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

생성물 1

HCID 86668143(S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide수율 46.3%

시약·촉매·용매 2

HCID 23925
Iron
촉매
HCID 111,2-Dichloroethane용매

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온도
50 °C

실험 절차

A mixture of (S)-6-(3-cyano-1-cyclobutyl-6-(difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (500 mg, 0.94 mmol), Fe powder (700 mg, 13 mmol), Br2 (300 μL, 5.9 mmol), and 1,2-dichloroethane (3 mL) was heated at 50° C. for 3 hours. The reaction mixture was then poured into aq. NaHSO3 solution. This was extracted into CH2Cl2. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under vacuum. Purification by silica gel chromatography (ethyl acetate in hexanes, 20% to 30%) yielded (S)-6-(4-bromo-3-cyano-1-cyclobutyl-6 (difluoromethoxy)-5-fluoro-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (266 mg, 46%) as a white solid.

후처리

  1. extractionThis was extracted into CH2Cl2
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under vacuum
  5. customPurification by silica gel chromatography (ethyl acetate in hexanes, 20% to 30%)

출처 및 근거

ORD 기록
ord-7dc2258f4f0542ec90a444b0eaa2e784
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08735414B2

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