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 1159999Notes

Reaction equation

HRID 1159999 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

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]+.

Workup

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

Sources & evidence

ORD record
ord-81ba8cde4d2c4bec8281024ffe614919
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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