Hydrochloric Acid → (S)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoic acid

HRID 75833Notes

Reaction equation

HRID 75833 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:32])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:21]=[C:20]([C:22]([NH:24][C@@H:25]([CH2:30][OH:31])[C:26]([O:28]C)=[O:27])=[O:23])[O:19][N:18]=2)=[CH:13][CH:12]=1.CC(C)C(NC(C1ON=C(C2C=CC(NC(NC3C=CC(C(F)(F)F)=CC=3)=O)=CC=2)C=1)=O)C(OC)=O.O.[OH-].[Li+].Cl>C1COCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:32])[NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:21]=[C:20]([C:22]([NH:24][C@@H:25]([CH2:30][OH:31])[C:26]([OH:28])=[O:27])=[O:23])[O:19][N:18]=2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67352407Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoateHCID 67352794(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate

Product 1

HCID 67353556(S)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoic acidYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoate (compound of Example 275, 200 mg, 0.452 mmol) was dissolved in THF and water in 2:1 ratio. Lithium hydroxide monohydrate (29 mg, 0.678 mmol) was added and the reaction mixture was stirred at RT for 4 hours. The reaction mixture was acidified with dilute HCl and extracted with EtOAc. Organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure. Crude compound was purified by washing with methanol to get 85 mg (44%) of the title compound. MS: ES (−): m/z 427 (M−1); ES (+): m/z 429(M+1); 1HNMR (DMSO-d6, 300 MHz): δ 9.377 (s, 1H), 8.885 (d, 1H), 8.701 (s, 1H), 8.178 (t, 1H), 7.892 (d, 2H), 7.692 (s, 1H), 7.641 (d, 2H), 7.289 (m, 1H), 7.188 (t, 1H), 7.066 (m, 1H), 4.492 (m, 1H), 3.868 (m, 2H), 3.554 (m, 1H), 3.087 (s, 3H).

Workup

  1. extractionextracted with EtOAc
  2. customOrganic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customCrude compound was purified
  6. washby washing with methanol

Sources & evidence

ORD record
ord-e072460a403343d08f487d11b723860d
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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