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

HRID 1159895Notes

Reaction equation

HRID 1159895 reaction equation
FC(F)(F)C([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([NH:15][C:16]3[N:21]=[C:20]([C:22]4[C:23]([C:31]5[CH:32]=[C:33]([NH:37][C:38](=[O:45])[C:39]6[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=6)[CH:34]=[CH:35][CH:36]=5)=[N:24][N:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=45)[CH:19]=[CH:18][N:17]=3)=[CH:10][CH:11]=2)[CH2:6]1)=O.O[Li].O>C1COCC1.O>[CH2:6]1[C:7]2[C:12](=[CH:11][CH:10]=[C:9]([NH:15][C:16]3[N:21]=[C:20]([C:22]4[C:23]([C:31]5[CH:32]=[C:33]([NH:37][C:38](=[O:45])[C:39]6[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=6)[CH:34]=[CH:35][CH:36]=5)=[N:24][N:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=45)[CH:19]=[CH:18][N:17]=3)[CH:8]=2)[CH2:13][CH2:14][NH:5]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59513753HCID 59513753, compound

Product 1

HCID 59513880N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamideYield 101.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{3-[3-(2-{[2-(2,2,2-Trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamide (191 mg, 0.30 mmol) in THF (4.0 mL) was added a solution of LiOH.H2O (19.8 mg, 0.47 mmol) in H2O (1.5 mL). The mixture was stirred at rt for 30 min. The mixture was partitioned between saturated aq. NaHCO3 and 5:1 CHCl3/isopropanol. The organic layer was separated, dried over Na2SO4, filtered and concentrated to give 191 mg of crude product. Purification by silica gel chromatography (0 to 40% sat. ammonia/MeOH in EtOAc) afforded 163.2 mg of the title compound as a white powder. LCMS ((ES)+ 538.3. 1H NMR (400, DMSO-d6) δ 2.63 (t, 2H, J=5.6), 2.96 (t, 2H, J=5.6), 3.80 (s, 2H), 6.46 (d, 1H, J=5.2), 6.95 (d, 1H, J-=8.4), 7.11 (t, 1H, J=6.4), 7.29 (d, 1H, J=8.0), 7.36 (d, 1H, J=9.2), 7.43-7.57 (m, 5H), 7.93 (d, 2H, J=7.2), 8.09 (s, 1H), 8.21 (d, 1H, J=5.6), 8.49 (d, 1H, J=8.8), 8.82 (d, 1H, J=6.8), 9.41 (s, 1H), 10.37 (s, 1H).

Workup

  1. customThe mixture was partitioned between saturated aq. NaHCO3 and 5:1 CHCl3/isopropanol
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give 191 mg of crude product
  7. customPurification by silica gel chromatography (0 to 40% sat. ammonia/MeOH in EtOAc)

Sources & evidence

ORD record
ord-fbdfe5eb4bdb480282fecf8c15432510
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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