Lithium hydroxide, monohydrate → N-{4-[2-(3-Aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine

HRID 1159999ノート

反応式

HRID 1159999 の反応式
FC(F)(F)C([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]4[CH:37]=[C:36]5[C:31]([CH2:32][CH2:33][N:34]([CH3:38])[CH2:35]5)=[CH:30][CH:29]=4)[N:22]=3)=[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][N:14]3[N:13]=2)[CH:7]=1)=O.O[Li].O>O1CCCC1.O.C(Cl)Cl>[NH2:5][C:6]1[CH:7]=[C:8]([C:12]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]4[CH:37]=[C:36]5[C:31]([CH2:32][CH2:33][N:34]([CH3:38])[CH2:35]5)=[CH:30][CH:29]=4)[N:22]=3)=[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][N:14]3[N:13]=2)[CH:9]=[CH:10][CH:11]=1

参加物

6

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 595137262,2,2-Trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamide

生成物 1

HCID 59511387N-{4-[2-(3-Aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine収率 92%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of 2,2,2-trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamide (290 mg, 0.53 mmol) in tetrahydrofuran (2 mL) and deionized water (2 mL) was added LiOH.H2O (34 mg, 0.80 mmol). The reaction was heated to 50° C. for 3 h, and then diluted with 10 mL DCM. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and concentrated to generate the title compound in 92% yield (219 mg, 0.49 mmol). 1H NMR (400 MHz, d6-DMSO) δ 9.41 (s, 1H), 8.79 (d, J=6.8 Hz, 1H), 8.52 (bd, 1H), 8.21 (d, J=5.3 Hz, 1H), 7.53 (s, 1H), 7.41-7.46 (m, 2H), 7.08-7.15 (m, 2H), 7.00 (d, J=8.2 Hz, 1H), 6.80 (s, 1H), 6.67 (t, J=7.7 Hz, 1H), 6.49 (d, J=5.3 Hz, 1H), 5.25 (s, 2H), 3.42 (s, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.58 (t, J=5.7 Hz, 2H), 2.32 (s, 3H). MS (ESI) m/z=448 [M+H]+.

後処理

  1. extractionThe aqueous layer was extracted with EtOAc
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-81ba8cde4d2c4bec8281024ffe614919
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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