Lithium hydroxide, monohydrate → 2,6-Difluoro-N-{3-[3-(2-{[3-({[2-(methylsulfonyl)ethyl]amino}methyl)-phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamide

HRID 1159997Notes

Reaction equation

HRID 1159997 reaction equation
[F:1][C:2]1[CH:52]=[CH:51][CH:50]=[C:49]([F:53])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][N:36]([CH2:43][CH2:44][S:45]([CH3:48])(=[O:47])=[O:46])C(=O)C(F)(F)F)[CH:30]=4)[N:23]=3)=[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][N:15]3[N:14]=2)[CH:8]=1)=[O:5].O[Li].O>C1COCC1.O.CCOC(C)=O>[F:53][C:49]1[CH:50]=[CH:51][CH:52]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][NH:36][CH2:43][CH2:44][S:45]([CH3:48])(=[O:47])=[O:46])[CH:30]=4)[N:23]=3)=[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][N:15]3[N:14]=2)[CH:8]=1)=[O:5]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 595136862,6-difluoro-N-[3-(3-{2-[(3-{[[2-(methylsulfonyl)ethyl](trifluoro-acetyl)amino]methyl}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

Product 1

HCID 595138742,6-Difluoro-N-{3-[3-(2-{[3-({[2-(methylsulfonyl)ethyl]amino}methyl)-phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}benzamideYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2,6-difluoro-N-[3-(3-{2-[(3-{[[2-(methylsulfonyl)ethyl](trifluoro-acetyl)amino]methyl}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide (102 mg, 0.14 mmol) in THF (3 mL) and water (0.5 mL) was added LiOH.H2O (12 mg, 0.28 mmol). The solution was stirred at 50° C. for 1 h, then diluted with 25 mL EtOAc and washed with 1 M aqueous Na2CO3. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and lyophilized to generate 42 mg of the title compound as a yellow powder (77 mg, 84% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.95 (s, 1H), 9.55 (s, 1H), 8.86 (d, J=6.6 Hz, 1H), 8.52 (d, J=8.2 Hz, 1H), 8.27 (d, J=5.0 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.75 (s, 1H), 7.59 (d, J=7.3 Hz, 1H), 7.50 (bs, 2H), 7.37 (d, J=7.5 Hz, 1H), 7.27 (d, J=7.7 Hz, 1H), 7.22 (t, J=8.1 Hz, 1H), 7.13-7.18 (m, 4H), 6.93 (d, J=6.9 Hz, 1H), 6.53 (d, J=5.5 Hz, 1H), 3.67 (s, 2H), 3.23 (bs, 2H), 3.01 (s, 3H), 2.87-2.91 (m, 2H). MS (ESI) m/z=654 [M+H]+.

Workup

  1. washwashed with 1 M aqueous Na2CO3
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered

Sources & evidence

ORD record
ord-06b9e4efc47f4fb09008cfb2d0c71062
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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