Hydrochloric Acid → 2,6-Difluoro-N-{2-fluoro-5-[3-(2-{[2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamide

HRID 1159962Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1159962
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([F:34])=[C:21]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[NH2:35][C:36]1[CH:45]=[C:44]2[CH:39]([CH2:40][CH2:41][N:42]([C:46](=[O:51])[C:47]([F:50])([F:49])[F:48])[CH2:43]2)[CH2:38][CH:37]=1.Cl>O1CCOCC1.CC(O)C>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[C:24]([NH:23][C:21]1[CH:22]=[C:17]([C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:35][C:36]4[CH:45]=[C:44]5[C:39]([CH2:40][CH2:41][N:42]([C:46](=[O:51])[C:47]([F:50])([F:48])[F:49])[CH2:43]5)=[CH:38][CH:37]=4)[N:7]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)[CH:18]=[CH:19][C:20]=1[F:34])=[O:33]

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 59513873N-{5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-fluorophenyl}-2,6-difluorobenzamideHCID 866187817-amino-N-trifluoroacetyl tetrahydroisoquinoline

Produkt 1

HCID 595138152,6-Difluoro-N-{2-fluoro-5-[3-(2-{[2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamideAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of N-{5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-fluorophenyl}-2,6-difluorobenzamide (162 mg, 0.34 mmol) in 1,4-dioxane (6 mL) and 2-propanol (2 mL) was added 7-amino-N-trifluoroacetyl tetrahydroisoquinoline (165 mg, 0.68 mmol) followed by catalytic 12M HCl. After heating overnight at 80° C., reaction was quenched with saturated NaHCO3 (25 mL), solvent removed by rotary evaporation, aqueous layer extracted with DCM (25 mL), organic layer concentrated, and purified by column chromatography (5-50% EtOAc in hexanes) to provide the product (109 mg, 47%) as an off-white solid. ESIMS (M+H)+=688.

Aufarbeitung

  1. customreaction
  2. customwas quenched with saturated NaHCO3 (25 mL), solvent
  3. customremoved by rotary evaporation, aqueous layer
  4. extractionextracted with DCM (25 mL), organic layer
  5. concentrationconcentrated
  6. custompurified by column chromatography (5-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e744919fc2384751a437473ef09ba5df
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812022B2

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