Hydrochloric Acid → HCID 59441720, Verbindung

HRID 1014432

Reaktionsgleichung

Reaktionsgleichung von HRID 1014432
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[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.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH2:47])[CH:45]=2)[CH2:40][CH2:39]1)=[O:37])[CH3:34].Cl.O1CCOCC1>FC(F)(F)CO.[NH4+].[OH-].C1COCC1>[CH3:32][N:33]([CH3:34])[CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH:47][C:2]3[N:3]=[C:4]([NH:21][C:22]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=4[C:24]([NH2:26])=[O:25])[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=5)(=[O:13])=[O:12])[C:6]=4[N:7]=3)[CH:45]=2)[CH2:40][CH2:39]1)=[O:37]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 86644188HCID 86644188, Verbindung

Produkt 1

HCID 59441720HCID 59441720, VerbindungAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 64092,2,2-TrifluoroethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 14923Ammonium HydroxideLösungsmittel

Versuchsvorschrift

A mixture of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (11 g, 24 mmol), 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (5 g, 20 mmol), a 4M HCl solution in dioxane (25 mL, 100 mmol) and 2,2,2-trifluoroethanol (250 mL) was heated at 80° C. for 16 h. The resulting mixture was allowed to cool to rt and diluted with a 27% aqueous NH4OH solution (250 mL) and THF (250 mL). The reaction mixture was stirred at rt overnight. The resulting slurry was filtered and the solids were triturated using H2O (300 mL), Et2O (300 mL) and finally EtOAc (300 mL). The solids were dissolved in THF, concentrated onto Celite and purified by silica gel chromatography using 0-10% MeOH (containing 0.2% NH3)/CH2Cl2. The solids obtained following chromatography were triturated using a mixture of MeOH and CH2Cl2to afford 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide as a beige solid (6.8 g, 51%).

Aufarbeitung

  1. filtrationThe resulting slurry was filtered
  2. customthe solids were triturated
  3. dissolutionThe solids were dissolved in THF
  4. concentrationconcentrated onto Celite
  5. custompurified by silica gel chromatography
  6. customThe solids obtained
  7. customwere triturated
  8. additiona mixture of MeOH and CH2Cl2to

Quellen und Nachweise

ORD-Eintrag
ord-6f4dab0240e74e02b912d78f19234777
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

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