Hydrochloric Acid → 2-(3-(4-(3-(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)propanoic acid

HRID 75807Notes

Reaction equation

HRID 75807 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:33])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:22]=[C:21]([C:23]([NH:25][CH:26]([CH3:31])[C:27]([O:29]C)=[O:28])=[O:24])[O:20][N:19]=2)=[CH:14][C:13]=1[CH3:32].[Li+].[OH-].Cl>C1COCC1.O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[NH:9][C:10](=[O:33])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:22]=[C:21]([C:23]([NH:25][CH:26]([CH3:31])[C:27]([OH:29])=[O:28])=[O:24])[O:20][N:19]=2)=[CH:14][C:13]=1[CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67353466Methyl 2-(3-(4-(3-(2,6-difluorophenyl)ureido)-3-methylphenyl) isoxazole-5-carboxamido)propanoate

Product 1

HCID 673524292-(3-(4-(3-(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)propanoic acidYield 43%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A mixture of Methyl 2-(3-(4-(3-(2,6-difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)propanoate (Example 101) (1.0 equiv.) and LiOH (3.0 equiv.) in 25 ml of 4:1 THF/water was stirred at room temperature for 15 min. The mixture was slightly acidified to pH <7 by adding 2N HCl and then the solvent was evaporated. The solid was suspended in water and filtered, given water washings and air-dried. The resulting solid was triturated with acetone and methanol and collected by filtration. This yielded the title compound as a white solid (43%) after drying in vacuo; 1H NMR (300 MHz, DMSO-d6) δ: 1.38-1.40 (d, J=7.2 Hz, 3H), 2.32 (s, 3H), 4.38-4.43 (m, 1H), 7.12-7.18 (m, 2H), 7.27-7.32 (m, 1H), 7.60 (S, 1H), 7.67-7.70 (d, J=8.4 Hz, 1H), 7.76 (s, 1H), 8.05-8.08 (d, J=8.7 Hz, 1H), 832 (s, 1H), 8.65 (s, 1H), 9.18-9.21 (d, J=7.2 Hz, 1H), 12.76 (brs, 1H); ms (ESI) m/z 445.1 [M+H]+.

Workup

  1. customthe solvent was evaporated
  2. filtrationfiltered
  3. customair-dried
  4. customThe resulting solid was triturated with acetone and methanol
  5. filtrationcollected by filtration

Sources & evidence

ORD record
ord-33dd513f1a6d4c9085b1961bd380eecc
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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