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

Reaktionsgleichung

Reaktionsgleichung von HRID 1014437
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]

Komponenten

7

Edukt 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

Produkt 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)benzamideAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 64092,2,2-TrifluoroethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-02ca086518de43f5adcf57908a369e47
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

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