Lithium Hydroxide → (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acid

HRID 221913Notes

Reaction equation

HRID 221913 reaction equation
C([O:3][C:4](=[O:38])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)=[CH:23][CH:22]=3)=[O:19])=[CH:15][C:14]([C:34]([CH3:37])([CH3:36])[CH3:35])=[N:13]2)=[CH:8][CH:7]=1)C.[Li+].[OH-]>C1COCC1.O.CCO.Cl>[C:34]([C:14]1[CH:15]=[C:16]([NH:17][C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[CH:23][CH:22]=2)=[O:19])[N:12]([C:9]2[CH:8]=[CH:7][C:6]([CH2:5][C:4]([OH:38])=[O:3])=[CH:11][CH:10]=2)[N:13]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 11692020ethyl (4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetate

Product 1

HCID 11496770(4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetic acidYield 92%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

To a suspension of ethyl(4-{3-tert-butyl-5-[({[4-(pyridin-4-yloxy)phenyl]-amino}carbonyl)amino]-1H-pyrazol-1-yl}phenyl)acetate (2.42 g, 4.72 mmol) in THF/H2O/EtOH (3:1:1, 50 mL) was added LiOH (0.34 g, 14.15 mmol) and the resulting reaction mixture was stirred at room temperature for 2.5 h. The mixture was evaporated at reduced pressure to afford a syrup-type residue. The residue was dissolved in 1N HCl, and then the acidity was adjusted to pH ˜7. The mixture was washed with EtOAc, and then the aqueous phase was acidified to pH 5-6. The white precipitate that formed was collected by filtration, washed with water and hexane, and air-dried to afford the product as a white solid (2.1 g) in 92% yield. 1H-NMR (DMSO-d6) δ 12.45 (broad, 1H), 9.64 (broad, 1H), 8.98 (broad, 1H), 8.38 (dd, JJ=1.6 Hz, 4.7 Hz, 2H), 7.51-7.42 (m, 4H), 7.36 (d, J=8.3 Hz, 2H), 7.05 (dd, JJ=2.1 Hz, 6.9 Hz, 2H), 6.84 (dd, JJ=1.6 Hz, 4.7 Hz, 2H), 6.31 (s, 1H), 3.58 (s, 2H), 1.27 (s, 9H); MS LC-MS [M+H]+=486.2, RT=2.39 min.

Workup

  1. customthe resulting reaction mixture
  2. customThe mixture was evaporated at reduced pressure
  3. customto afford a syrup-type residue
  4. washThe mixture was washed with EtOAc
  5. customThe white precipitate that formed
  6. filtrationwas collected by filtration
  7. washwashed with water and hexane
  8. customair-dried

Sources & evidence

ORD record
ord-46385965a89c4d48a6019c32a396dc96
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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