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 1685197노트

반응식

HRID 1685197 반응식
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

참가 물질

4

반응물 3

HCID 887Methanol2회HCID 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

생성물 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)-one수율 60%

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-6e1981659b6b407bbd322d7765fc54b1
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148387B2

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