Water → HCID 59513773, compound

HRID 1159996Notes

Reaction equation

HRID 1159996 reaction equation
[F:1][C:2]1[CH:52]=[CH:51][C:50]([F:53])=[CH:49][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.O[Li].O>C1COCC1.CO.CCOC(C)=O>[F:1][C:2]1[CH:52]=[CH:51][C:50]([F:53])=[CH:49][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

7

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59513858HCID 59513858, compound

Product 1

HCID 59513773HCID 59513773, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2,5-difluoro-N-[3-(3-{2-[(3-{[[2-(methylsulfonyl)ethyl]-(trifluoroacetyl)amino]methyl}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide (104 mg, 0.14 mmol) in THF (3 mL), MeOH (0.5 mL), and water (0.5 mL) was added LiOH.H2O (12 mg, 0.28 mmol). The solution was stirred at 50° C. for 4 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 concentrated. The crude product was purified by flash chromatography to generate 42 mg of the title compound as a yellow solid (67 mg, 73% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.65 (s, 1H), 9.55 (s, 1H), 8.85 (d, J=6.7 Hz, 1H), 8.54 (d, J=8.8 Hz, 1H), 8.26 (d, J=5.2 Hz, 1H), 8.04 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.76 (s, 1H), 7.60 (d, J=7.9 Hz, 1H), 7.42-7.55 (m, 5H), 7.36 (d, J=7.8 Hz, 1H), 7.20 (t, J=7.9 Hz, 1H), 7.14 (t, J=6.8 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 6.51 (d, J=5.3 Hz, 1H), 3.67 (s, 2H), 3.23 (t, J=6.6 Hz, 2H), 3.01 (s, 3H), 2.91 (t, J=6.6 Hz, 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
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-16169506c8ed4509a4a15418a347ddec
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

Loading…