Hydrochloric Acid → 2,6-Difluoro-N-{2-(methyloxy)-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 1159957

Reaktionsgleichung

Reaktionsgleichung von HRID 1159957
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[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.[NH2:36][C:37]1[CH:46]=[C:45]2[CH:40]([CH2:41][CH2:42][N:43]([C:47](=[O:52])[C:48]([F:51])([F:50])[F:49])[CH2:44]2)[CH2:39][CH:38]=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:36][C:37]4[CH:46]=[C:45]5[C:40]([CH2:41][CH2:42][N:43]([C:47](=[O:52])[C:48]([F:51])([F:49])[F:50])[CH2:44]5)=[CH:39][CH:38]=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[O:34][CH3:35])=[O:33]

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 59513745N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzamideHCID 866187817-amino-N-trifluoroacetyl tetrahydroisoquinoline

Produkt 1

HCID 595136612,6-Difluoro-N-{2-(methyloxy)-5-[3-(2-{[2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamideAusbeute 44,7 %

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-(methyloxy)phenyl]-2,6-difluorobenzamide (158 mg, 0.32 mmol) in 1,4-dioxane (6 mL) and 2-propanol (2 mL) was added 7-amino-N-trifluoroacetyl tetrahydroisoquinoline (158 mg, 0.64 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), the organic layer was concentrated and purified by column chromatography (5-50% EtOAc in hexanes) to provide the product (100 mg, 44%) as an off-white solid. ESIMS (M+H)+=700.

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)
  5. concentrationthe organic layer was concentrated
  6. custompurified by column chromatography (5-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-49ad52fb315249c888b1a4e1cc840300
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812022B2

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