Potassium Cyanide → 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetonitrile

HRID 1473186ノート

反応式

HRID 1473186 の反応式
CS(O[CH2:6][C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[N:15]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:16]=[CH:17][C:9]=2[C:8]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)(=O)=O.[C-:32]#[N:33].[K+]>CN(C)C=O>[CH2:18]([N:15]1[C:10]2[C:11](=[O:14])[N:12]([CH3:13])[C:7]([CH2:6][C:32]#[N:33])=[C:8]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)[C:9]=2[CH:17]=[CH:16]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

参加物

4

反応物 2

HCID 9032Potassium CyanideHCID 89463321(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)methyl methanesulfonate

生成物 1

HCID 894630402-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetonitrile収率 67%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A suspension of 1-benzyl-4-(4-chlorophenyl)-5-(hydroxymethyl)-6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (4 g, 10.6 mmol) in Dichloromethane (DCM) (50 mL) was treated with Et3N (4.38 mL, 31.5 mmol) and MsCl (1.839 mL, 23.60 mmol) at 0° C. and then stirred for 30 min. The mixture was diluted with Dichloromethane, washed with 0.1N HCl and NaHCO3, dried over Na2SO4, filtered and concentrated to afford (1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)methyl methanesulfonate as a pale yellow solid (4.8 g, 10.5 mmol, 95% yield) which was used for in next step without any further purification. A solution of (1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)methyl methanesulfonate (4.8 g, 10.5 mmol) in N,N-Dimethylformamide (DMF) (30 mL) was treated with KCN (6.15 g, 94 mmol) and the resultant was stirred at ambient temperature overnight. The mixture was quenched with water and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetonitrile (2.7 g, 7.0 mmol, 67% yield) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.47-7.52 (m, 2H) 7.31-7.35 (m, 3H) 7.27-7.30 (m, 4H) 7.04-7.09 (m, 1H) 5.94-5.98 (m, 1H) 5.83-5.88 (s, 2H) 3.81 (s, 3H) 3.64 (s, 2H); LCMS (m/z) ES+=388 (M+1).

後処理

  1. customwas used for in next step without any further purification
  2. customThe mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel (0-70% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-697afcd751924f6881e998c67a89530f
出典データセット
uspto-grants-2015_04
特許番号
US09012642B2

反応ノート

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