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 1159962노트

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HRID 1159962 반응식
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]

참가 물질

6

반응물 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

생성물 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}benzamide수율 47%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e744919fc2384751a437473ef09ba5df
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

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