Cesium fluoride → 3-chloro-N-(3-(3-(pyrrolidin-1-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide

HRID 330995노트

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HRID 330995 반응식
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[N:4]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=1.[N:30]1([C:35]2[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=2)[CH2:34][CH2:33][CH2:32][CH2:31]1.[F-].[Cs+].B(O)O>COCCOC>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[CH:7][N:6]=[C:5]3[N:4]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=[C:2]([C:37]4[CH:38]=[CH:39][CH:40]=[C:35]([N:30]5[CH2:31][CH2:32][CH2:33][CH2:34]5)[CH:36]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

참가 물질

6

반응물 4

HCID 25953Cesium fluoride2회HCID 61668Boronic AcidHCID 41926693-(Pyrrolidino)phenylboronic acidHCID 71090292N-[3-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide

생성물 1

HCID 710900743-chloro-N-(3-(3-(pyrrolidin-1-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide수율 48.7%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

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온도
120 °C

실험 절차

A mixture of N-[3-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide (D4) (233 mg, 0.451 mmol), [3-(1-pyrrolidinyl)phenyl]boronic acid (129 mg, 0.676 mmol), cesium fluoride (205 mg, 1.352 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (36.8 mg, 0.045 mmol) in DME (5.706 mL) was heated in a microwave at 120° C. for 30 minutes. Additional 3-(1-pyrrolidinyl)phenyl]boronic acid (129 mg, 0.676 mmol), cesium fluoride (68.3 mg) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (36.8 mg, 0.045 mmol) were added into the reaction mixture and heated in a microwave at 120° C. for 1 hour. The reaction mixture was partitioned between aqueous saturated NaHCO3 solution and ethyl acetate. The aqueous phase was separated and extracted with ethyl acetate (thrice). The organic extracts were combined, dried over phase separator. The residue was purified on silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane). The appropriate fractions were combined and evaporated to dryness to afford the title compound (128.1 mg). LCMS (A): m/z (M+H)+ 583, C29H35ClN4O3SSi requires 582 (acidic).

후처리

  1. temperatureheated in a microwave at 120° C. for 1 hour
  2. customThe reaction mixture was partitioned between aqueous saturated NaHCO3 solution and ethyl acetate
  3. customThe aqueous phase was separated
  4. extractionextracted with ethyl acetate (thrice)
  5. customdried over phase separator
  6. customThe residue was purified on silica gel
  7. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane)
  8. customevaporated to dryness

출처 및 근거

ORD 기록
ord-cd1b4e73760a43e79d1be596dd5e411a
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877742B2

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