Tributylphosphine → 4-((3-Chloro-4-fluorobenzyl)oxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203051ノート

反応式

HRID 2203051 の反応式
[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]=[C:29]([CH2:34]O)[CH:30]=[CH:31][C:32]=1[F:33].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>CCOC(C)=O.C1COCC1>[Cl:26][C:27]1[CH:28]=[C:29]([CH:30]=[CH:31][C:32]=1[F:33])[CH2:34][O: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])([CH3:20])[CH3:21])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[C:4](=[O:25])[CH:3]=1

参加物

7

反応物 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27736073-Chloro-4-fluorobenzyl alcoholHCID 1213862594-Hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

生成物 1

HCID 896911394-((3-Chloro-4-fluorobenzyl)oxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one収率 41.1%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

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), (3-chloro-4-fluorophenyl)methanol (95 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, washed with water and brine successively, dried over MgSO4, filtered through a plug of NH silica gel, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by NH silica gel column chromatography (hexane/EtOAc). Then the resulting solid was recrystallized from IPA-EtOAc to give the title compound (58.4 mg) as an off-white solid.

後処理

  1. washwashed with water and brine successively
  2. dry with materialdried over MgSO4
  3. filtrationfiltered through a plug of NH silica gel
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (hexane/EtOAc
  6. customThen the resulting solid was recrystallized from IPA-EtOAc

出典と根拠

ORDレコード
ord-a0b1ae215b044f76a1b9d4c276054649
出典データセット
uspto-grants-2016_06
特許番号
US09365540B2

反応ノート

読み込み中…