Methanol → 4-(4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one

HRID 1685197ノート

反応式

HRID 1685197 の反応式
Cl[C:2]1[C:3]2[CH2:10][C:9](=[O:11])[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=3[O:21][CH3:22])[C:4]=2[N:5]=[CH:6][N:7]=1.CO.Cl.Cl.[F:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:35]=[C:36]([CH:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)[N:37]([CH2:39][CH2:40][N:41]([CH3:43])[CH3:42])[CH:38]=2)=[CH:30][C:29]=1[C:50]([F:53])([F:52])[F:51]>>[CH3:42][N:41]([CH3:43])[CH2:40][CH2:39][N:37]1[CH:38]=[C:34]([C:31]2[CH:32]=[CH:33][C:28]([F:27])=[C:29]([C:50]([F:52])([F:51])[F:53])[CH:30]=2)[N:35]=[C:36]1[CH:44]1[CH2:45][CH2:46][N:47]([C:2]2[C:3]3[CH2:10][C:9](=[O:11])[N:8]([CH2:12][C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=4[O:21][CH3:22])[C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:48][CH2:49]1

参加物

4

反応物 3

HCID 887Methanol2 回HCID 569717344-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-oneHCID 866416122-(4-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine dihydrochloride

生成物 1

HCID 672649744-(4-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one収率 60%

実験手順

Combine a mixture of 4-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (1.10 equiv; 868.3 mmol; 277.63 g) in methanol (62.44 mol; 2.53 L) at RT, a solution of 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine dihydrochloride (1.00 equiv; 789.35 mmol; 361.0 g) and TEA (9077 mmol; 1265 mL) in methanol (62.44 mol; 2.53 L) and stir the mixture overnight at 55-60° C. Partition the reaction mixture between water (10 L) and EA (10 L). Extract the organic layer with 2 N HCl (5 L). Separate and extract the aqueous layer with EA (5 L). An oil separates in the aqueous layer. Decant the aqueous liquid and hold the oil for recovery of product. Stir the decanted aqueous layer with EA (5 L) and adjust the pH of the mixture to 10-11 with 2 N NaOH. Separate the organic layer, wash with brine, and dry over Na2SO4. Filter and evaporate the solvent to give the title compound (473.3 mmol; 316.0 g; 60%).

後処理

  1. customPartition the reaction mixture between water (10 L) and EA (10 L)
  2. extractionExtract the organic layer with 2 N HCl (5 L)
  3. customSeparate
  4. extractionextract the aqueous layer with EA (5 L)
  5. customDecant the aqueous liquid
  6. customSeparate the organic layer
  7. washwash with brine
  8. dry with materialdry over Na2SO4
  9. filtrationFilter
  10. customevaporate the solvent

出典と根拠

ORDレコード
ord-6e1981659b6b407bbd322d7765fc54b1
出典データセット
uspto-grants-2012_04
特許番号
US08148387B2

反応ノート

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