Sulfuric Acid → 2,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

HRID 1014437

반응식

HRID 1014437 반응식
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[C:23]=2[C:24]([NH2:26])=[O:25])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[CH3:33][CH:34]([N:36]1[CH2:41][CH2:40][N:39]([C:42]2[CH:48]=[CH:47][C:45]([NH2:46])=[C:44]([O:49][CH3:50])[CH:43]=2)[CH2:38][CH2:37]1)[CH3:35].[I-].[K+].S(=O)(=O)(O)O>C(O)C(F)(F)F.C1COCC1>[F:32][C:27]1[CH:28]=[C:29]([F:31])[CH:30]=[C:22]([NH:21][C:4]2[C:5]3[CH:10]=[CH:9][N:8]([S:11]([C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=4)(=[O:13])=[O:12])[C:6]=3[N:7]=[C:2]([NH:46][C:45]3[CH:47]=[CH:48][C:42]([N:39]4[CH2:40][CH2:41][N:36]([CH:34]([CH3:33])[CH3:35])[CH2:37][CH2:38]4)=[CH:43][C:44]=3[O:49][CH3:50])[N:3]=2)[C:23]=1[C:24]([NH2:26])=[O:25]

참가 물질

7

반응물 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 457907394-(4-Isopropylpiperazin-1-YL)-2-methoxyphenylamineHCID 866441962-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide

생성물 1

HCID 673173812,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide수율 38.2%

시약·촉매·용매 2

HCID 64092,2,2-Trifluoroethanol용매HCID 8028Tetrahydrofuran용매

실험 절차

A suspension of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide (2.71 g, 5.68 mmol), 4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)aniline (2.12 g, 8.52 mmol), potassium iodide (catalytic), and sulfuric acid (2.72 ml, 51 mmols) in trifluoroethanol (150 ml) was heated at 90C for 4 hrs. The reaction was diluted with 1:1 THF:ethyl acetate (300 ml) and washed with saturated NaHCO3 (300 ml). The organic layer was removed and concentrated by rotary evaporation. The solids were then added to THF (300 ml) followed by ammonium hydroxide (300 ml) and the resulting mixture was stirred at rt overnight. Next, the crude reaction was adsorbed to silica gel and purified by LC (DCM to 5% MeOH/DCM) to afford 2,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.5 g, 38% over two steps). ESIMS (M+H)+=691.

후처리

  1. washethyl acetate (300 ml) and washed with saturated NaHCO3 (300 ml)
  2. customThe organic layer was removed
  3. concentrationconcentrated by rotary evaporation
  4. additionThe solids were then added to THF (300 ml)
  5. customNext, the crude reaction
  6. custompurified by LC (DCM to 5% MeOH/DCM)

출처 및 근거

ORD 기록
ord-02ca086518de43f5adcf57908a369e47
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981903B2

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