Lithium hydroxide, monohydrate → HCID 59513851, compound

HRID 1159990Notes

Reaction equation

HRID 1159990 reaction equation
[F:1][C:2]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[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](C)[C:37](=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.C(Cl)Cl>[F:1][C:2]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[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][CH3:37])[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 59513812HCID 59513812, compound

Product 1

HCID 59513851HCID 59513851, compoundYield 45.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2,6-difluoro-N-[3-(3-{2-[(3-{[methyl(trifluoroacetyl)amino]-methyl}phenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide (70 mg, 0.11 mmol) in THF (3 mL) and water (0.5 mL) was added LiOH.H2O (10 mg, 0.21 mmol). The solution was stirred at 50° C. for two h, then diluted with 25 mL DCM and washed with 1 M aqueous Na2CO3. The aqueous layer was extracted with DCM, and the combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography to generate 26 mg of the title compound as a yellow solid (0.05 mmol, 42% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.95 (s, 1H), 9.52 (s, 1H), 8.86 (d, J=7.0 Hz, 1H), 8.52 (d, J=8.8 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=8.2 Hz, 1H), 7.73 (s, 1H), 7.46-7.62 (m, 4H), 7.36 (d, J=7.5 Hz, 1H), 7.12-7.28 (m, 4H), 6.92 (d, J=7.3 Hz, 1H), 6.53 (d, J=5.3 Hz, 1H), 3.59 (s, 2H), 2.26 (s, 3H). MS (ESI) m/z=562 [M+H]+.

Workup

  1. washwashed with 1 M aqueous Na2CO3
  2. extractionThe aqueous layer was extracted with DCM
  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-d1b7cea841874d548037928f45bc758c
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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