Lithium Hydroxide → 2,6-Difluoro-N-(2-(methyloxy)-5-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

HRID 1159958Notes

Reaction equation

HRID 1159958 reaction equation
[F:1][C:2]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:38]=[C:37]5[C:32]([CH2:33][CH2:34][N:35](C(=O)C(F)(F)F)[CH2:36]5)=[CH:31][CH:30]=4)[N:23]=3)=[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][N:15]3[N:14]=2)[CH:10]=[CH:9][C:8]=1[O:45][CH3:46])=[O:5].C1COCC1.[Li+].[OH-]>O>[F:51][C:47]1[CH:48]=[CH:49][CH:50]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:38]=[C:37]5[C:32]([CH2:33][CH2:34][NH:35][CH2:36]5)=[CH:31][CH:30]=4)[N:23]=3)=[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][N:15]3[N:14]=2)[CH:10]=[CH:9][C:8]=1[O:45][CH3:46])=[O:5]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 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}benzamide

Product 1

HCID 116858262,6-Difluoro-N-(2-(methyloxy)-5-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamideYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 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 (50 mg, 0.072 mmol) in 10:1 THF:H2O (10 mL) was added 1M LiOH (0.43 ml, 0.43 mmol) and the reaction mixture was heated at 50° C. overnight. The reaction was washed with brine (10 mL), organic layer removed, adsorbed to silica gel and purified by column chromatography (0-10% MeOH/DCM+1% NH4OH) to afford the title compound (32 mg, 74%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 2.75 (t, 2H, J=5.86 Hz), 3.13 (t, 2H, J=5.86 Hz), 3.93 (s, 3H), 3.97 (s, 2H), 6.64 (d, 1H, J=5.31 Hz), 6.86-6.89 (m, 1H), 6.94-7.03 (m, 4H), 7.24-7.44 (m, 5H), 8.16 (d, 1H, J=5.31 Hz), 8.32-8.38 (m, 2H), 8.50 (d, 1H, J=6.96 Hz), 8.98 (m, 1H); ESIMS (M+H)+=604.

Workup

  1. washThe reaction was washed with brine (10 mL), organic layer
  2. customremoved
  3. custompurified by column chromatography (0-10% MeOH/DCM+1% NH4OH)

Sources & evidence

ORD record
ord-0f2a84ecc2c64aa49e6c3bf108d2624e
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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