Hydrochloric Acid → [4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)-ureido]-pyridin-2-yl)-phenyl)-cyclohexyl]-acetic acid

HRID 1404261Notes

Reaction equation

HRID 1404261 reaction equation
C[O:2][C:3](=[O:38])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=4)=[O:25])=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.Cl>C1COCC1.O.[OH-].[Li+]>[F:36][C:34]([F:35])([F:37])[O:33][C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:24](=[O:25])[NH:23][C:20]2[CH:21]=[CH:22][C:17]([C:14]3[CH:15]=[CH:16][C:11]([CH:8]4[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:38])=[O:2])[CH2:10][CH2:9]4)=[CH:12][CH:13]=3)=[N:18][CH:19]=2)=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66615770[4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)-ureido]-pyridin-2-yl}-phenyl)-cyclohexyl]-acetic acid methyl ester

Product 1

HCID 57899110[4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)-ureido]-pyridin-2-yl)-phenyl)-cyclohexyl]-acetic acid

Reagents, catalysts & solvents 2

HCID 3939Lithium HydroxideSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To 210 mg (0.4 mmol) [4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)ureido]-pyridin-2-yl}-phenyl)-cyclohexyl]-acetic acid methyl ester in THF/H2O (10 mL; 4:1), 5 mL (4M) aqueous Lithium Hydroxide solution was added and the mixture stirred at 60° C. for 5 hours. Acidified with concentrated hydrochloric acid which precipitated the desired compound. Filtered and dried under vacuum to afford [4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)-ureido]-pyridin-2-yl}-phenyl)-cyclohexyl]-acetic acid, which was subsequently dissolved in methanol (5 mL) one equivalent of potassium hydroxide and 2 mL of H2O were added and the resulting mixture was stirred at 40° C. for 2 hours. Evaporated to dryness to afford [4-(4-{5-[3-(4-Trifluoromethoxy-phenyl)-ureido]-pyridin-2-yl}-phenyl)-cyclohexyl]-acetic acid as the potassium salt: 1H NMR (400 MHz, MeOD) ppm 1.03-1.14 (m, 2 H) 1.45 (td, J=12.57, 9.98 Hz, 2 H) 1.75-1.87 (m, 5H) 2.03 (d, J=7.07 Hz, 2 H) 2.37-2.47 (m, 1 H) 7.12 (d, J=8.34 Hz, 2 H) 7.21 (d, J=8.34 Hz, 2 H) 7.43-7.51 (m, 2 H) 7.64-7.73 (m, 3 H) 7.96 (dd, J=8.72, 2.65 Hz, 1 H) 8.58 (d, J=2.27 Hz, 1H); (M+H)+ 514.2.

Workup

  1. customprecipitated the desired compound
  2. filtrationFiltered
  3. customdried under vacuum

Sources & evidence

ORD record
ord-9fda9bacf284432db2ba983499de88ab
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

Loading…