(4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acid → N-[3-tert-butyl-1-[4-(2-hydroxyethyl)phenyl]-1H-pyrazol-5-yl]-N'-[4-(pyridin-4-yloxy)-phenyl]urea

HRID 221914Notes

Reaction equation

HRID 221914 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)=[O:12])[N:7]([C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34](O)=[O:35])=[CH:29][CH:28]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].B.S([O-])(OC)=O>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)=[CH:18][CH:19]=2)=[O:12])[N:7]([C:27]2[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][OH:35])=[CH:31][CH:32]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 11496770(4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acidHCID 178419217HCID 178419217, compound

Product 1

HCID 11518461N-[3-tert-butyl-1-[4-(2-hydroxyethyl)phenyl]-1H-pyrazol-5-yl]-N'-[4-(pyridin-4-yloxy)-phenyl]ureaYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}-carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acid (100 mg, 0.21 mmol) in THF (4 mL) was added borane-methyl sulfite complex (0.51 mL, 2M in THF) drop-wise with stirring at room temperature. The resulting reaction mixture was heated at reflux for 2 h, then cooled to room temperature and quenched by the addition of EtOH/1N HCl. The resulting mixture was heated at reflux for 1 h. The mixture was cooled to room temperature and evaporated at reduced pressure, and the residue was dissolved in a mixture of EtOAc and saturated NaHCO3. The organic phase was dried over Na2SO4, concentrated, and purified by MPLC (50:50 hexane/EtOAc). The desired product was obtained as a white solid (50 mg) in 51% yield. 1H-NMR (DMSO-d6) δ 9.12 (s, 1H), 8.39 (m, 3H), 7.48 (d, J=9.0 Hz, 2H), 7.40-7.33 (m, 4H), 7.07 (d, J=8.8 Hz, 2H), 6.85 (m, 2H), 6.34 (s, 1H), 4.69 (t, J=5.1 Hz, 1H), 3.64 (m, 2H), 2.78 (t, J=7.1 Hz, 2H), 1.27 (s, 9H); MS LC-MS [M+H]+=472.2, RT=2.35 min.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux for 2 h
  4. temperaturecooled to room temperature
  5. customquenched by the addition of EtOH/1N HCl
  6. temperatureThe resulting mixture was heated
  7. temperatureat reflux for 1 h
  8. temperatureThe mixture was cooled to room temperature
  9. customevaporated at reduced pressure
  10. dissolutionthe residue was dissolved in a mixture of EtOAc and saturated NaHCO3
  11. dry with materialThe organic phase was dried over Na2SO4
  12. concentrationconcentrated
  13. custompurified by MPLC (50:50 hexane/EtOAc)

Sources & evidence

ORD record
ord-9e9180f18b2a409d9974f104934b76fa
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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