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 1159962ノート

反応式

HRID 1159962 の反応式
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]

参加物

6

反応物 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

生成物 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}benzamide収率 47%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e744919fc2384751a437473ef09ba5df
出典データセット
uspto-grants-2010_10
特許番号
US07812022B2

反応ノート

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