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ノート

反応式

HRID 1014437 の反応式
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]

参加物

7

反応物 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

生成物 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)benzamide収率 38.2%

試薬・触媒・溶媒 2

HCID 64092,2,2-Trifluoroethanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-02ca086518de43f5adcf57908a369e47
出典データセット
uspto-grants-2011_07
特許番号
US07981903B2

反応ノート

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