Lithium hydroxide, monohydrate → HCID 59513860, compound

HRID 1159992Notes

Reaction equation

HRID 1159992 reaction equation
[F:1][C:2]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][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]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>[NH2:36][CH2:35][C:31]1[CH:30]=[C:29]([NH:28][C:24]2[N:23]=[C:22]([C:21]3[C:13]([C:9]4[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]5[CH:43]=[C:44]([F:47])[CH:45]=[CH:46][C:2]=5[F:1])[CH:12]=[CH:11][CH:10]=4)=[N:14][N:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=34)[CH:27]=[CH:26][N:25]=2)[CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59513871HCID 59513871, compound

Product 1

HCID 59513860HCID 59513860, compoundYield 57.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2,5-difluoro-N-[3-(3-{2-[(3-{[(trifluoroacetyl)amino]methyl}phenyl)-amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide (90 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 2 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 (0.08 mmol, 55% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.66 (s, 1H), 9.55 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.54 (d, J=8.8 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.05 (s, 1H), 7.87 (d, J=7.7 Hz, 1H), 7.77 (s, 1H), 7.35-7.59 (m, 7H), 7.11-7.23 (m, 2H), 6.97 (d, J=7.5 Hz, 1H), 6.51 (d, J=4.9 Hz, 1H), 3.72 (s, 2H). MS (ESI) m/z=548 [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-45113b83d03b4143a6be2c210a6199b1
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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