2,2-Dimethylsuccinic anhydride → N-[4-(3-tert-butyl-5-{3-[4-(pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-phenyl]-2,2-dimethyl-succinamic acid

HRID 1174867Notes

Reaction equation

HRID 1174867 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([NH:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)=[O:15])=[CH:11][C:10]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:9]2)=[CH:4][CH:3]=1.[CH3:34][C:35]1([CH3:42])[CH2:40][C:39](=[O:41])[O:38][C:36]1=[O:37]>C1COCC1.CCOCC>[C:30]([C:10]1[CH:11]=[C:12]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)=[CH:19][CH:18]=2)=[O:15])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:39](=[O:41])[CH2:40][C:35]([CH3:42])([CH3:34])[C:36]([OH:38])=[O:37])=[CH:3][CH:4]=2)[N:9]=1)([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 536301891-[2-(4-aminophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)phenyl]urea

Product 1

HCID 11519796N-[4-(3-tert-butyl-5-{3-[4-(pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-phenyl]-2,2-dimethyl-succinamic acidYield 85%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1-[2-(4-amino-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea (208 mg, 0.47 mmol) and 2,2-dimethylsuccinic anhydride (66 mg, 0.52 mmol, 1.1 eq) in 2 mL THF was stirred at room temperature overnight. HPLC analysis indicated that starting material was remaining. The reaction was then heated at 60° C. for 2 days, at which time HPLC analysis indicated the reaction was complete. The reaction mixture was cooled to room temperature, and the resulting suspension was diluted with Et2O. The solid was isolated by filtration to afford the desired product (227 mg, 85%). 1H-NMR (DMSO-d6) δ 12.06 (s, 1H), 10.06 (s, 1H), 9.09 (s, 1H), 8.40 (d, J=6.0 Hz, 2H), 8.31 (s, 1H), 7.69 (d, J=9.0 Hz, 2H), 7.47 (d, J=9.0 Hz, 2H), 7.39 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 6.85 (dd, J=1.5 & 4.7 Hz, 2H), 6.33 (s, 1H), 2.59 (s, 2H), 1.26 (s, 9H), 1.21 (s, 6H); MS LC-MS [M+H]+=571.3, RT=2.49 min.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-1056ec1e408541f181c91e60d41cc03b
Source dataset
uspto-grants-2010_11
Patent number
US07838524B2

Reaction notes

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