Tributylphosphine → 4-((5-Chloropyridin-2-yl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203032노트

반응식

HRID 2203032 반응식
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([CH:16]4[CH2:18][CH:17]4[C:19]([OH:22])([CH3:21])[CH3:20])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[C:4](=[O:25])[CH:3]=1.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:33]O)=[N:31][CH:32]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>CCOC(C)=O.C1COCC1>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:33][O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[CH:10][C:11]4[N:15]=[C:14]([CH:16]5[CH2:18][CH:17]5[C:19]([OH:22])([CH3:20])[CH3:21])[N:13]([CH3:23])[C:12]=4[CH:24]=3)[C:4](=[O:25])[CH:3]=2)=[N:31][CH:32]=1

참가 물질

7

반응물 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 20537893(5-Chloropyridin-2-yl)methanolHCID 1213862594-Hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

생성물 1

HCID 897024424-((5-Chloropyridin-2-yl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one수율 49.9%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

To a mixture of 4-hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (100 mg), (5-chloropyridin-2-yl)methanol (85 mg), tributylphosphine (0.219 ml) and THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (223 mg), and the mixture was stirred at 60° C. for 2 h. The reaction mixture was diluted with EtOAc, quenched with water, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, filtered through silica pad, and concentrated in vacuo. The residue was purified by column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by recrystallization from IPA-IPE to give the title compound (68.4 mg) as an off-white solid.

후처리

  1. customquenched with water
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with water and brine successively
  5. dry with materialdried over MgSO4
  6. filtrationfiltered through silica pad
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (hexane/EtOAc
  9. customEtOAc/MeOH), followed by recrystallization from IPA-IPE

출처 및 근거

ORD 기록
ord-e39174d601204d0987dd6c273eb42974
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365540B2

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