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

반응식

HRID 1159957 반응식
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]

참가 물질

6

반응물 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

생성물 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}benzamide수율 44.7%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

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.

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

출처 및 근거

ORD 기록
ord-49ad52fb315249c888b1a4e1cc840300
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

연결된 노트

불러오는 중…