Water → 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-[2-fluoro-4-(2-methyl-Pyridin-4-yloxy)-phenyl)-urea

HRID 221909Notes

Reaction equation

HRID 221909 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=4)=[CH:21][C:20]=3[F:33])=[O:17])=[CH:13][C:12]([C:34]([CH3:37])([CH3:36])[CH3:35])=[N:11]2)=[CH:6][CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>C1COCC1>[C:34]([C:12]1[CH:13]=[C:14]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=3)=[CH:21][C:20]=2[F:33])=[O:17])[N:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:3][OH:2])=[CH:5][CH:6]=2)[N:11]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 536301844-(3-Tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid methyl ester

Product 1

HCID 115332541-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-[2-fluoro-4-(2-methyl-Pyridin-4-yloxy)-phenyl)-ureaYield 90.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(3-tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid methyl ester (700 mg, 1.35 mmol) in anhydrous THF at 0° C. was slowly added a 1N solution of lithium aluminum hydride in THF (0.95 mL, 0.95 mmol). The mixture was stirred at room temperature for 15 minutes, and then water was added dropwise to quench the reaction. The mixture was extracted with EtOAc, and the combined organic phases were dried over MgSO4 and evaporated at reduced pressure. The residue was purified by HPLC (10% to 90% aq acetonitrile) to afford 600 mg (90%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 8.97 (s, 1H), 8.79 (s, 1H), 8.29 (d, J=5.7 Hz, 1H), 8.13 (t, J=9.0 Hz, 1H), 7.46 (m, 4H), 7.18 (d, J=14.7 Hz, 1H), 6.95 (d, J=10.2 Hz, 1H), 6.76 (d, J=2.1 Hz, 1H), 6.71 (d, J=5.4 Hz, 1H), 6.36 (s, 1H), 5.30 (t, J=5.7 Hz, 2H), 2.38 (s, 3H), 1.25 (s, 9H); MS LC-MS [M+H]+=490.2, RT=2.41 min.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialthe combined organic phases were dried over MgSO4
  5. customevaporated at reduced pressure
  6. customThe residue was purified by HPLC (10% to 90% aq acetonitrile)

Sources & evidence

ORD record
ord-2e8649e899a14ea0b19c47f0cc5765c6
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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