Ammonia → 2-(2,6-Difluorophenyl)-5-(phenylamino)oxazole-4-carboxamide

HRID 389747Notes

Reaction equation

HRID 389747 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][C:11]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([C:14](O)=[O:15])[N:13]=1.O.OC1C2N=N[NH:31]C=2C=CC=1.CN(C)CCCN=C=NCC.N.O1CCOCC1>C(Cl)Cl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[O:10][C:11]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([C:14]([NH2:31])=[O:15])[N:13]=1

Participants

7

Reactant 5

HCID 222Ammonia2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 312751,4-Dioxane2×HCID 595875432-(2,6-Difluorophenyl)-5-(phenylamino)oxazole-4-carboxylic acidHCID 178526939HCID 178526939, compound

Product 1

HCID 595876212-(2,6-Difluorophenyl)-5-(phenylamino)oxazole-4-carboxamideYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2,6-difluorophenyl)-5-(phenylamino)oxazole-4-carboxylic acid (0.030 g, 0.095 mmol) in DCM (3 mL) was added hydroxybenzotriazole monohydrate (0.015 g, 0.098 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (0.020 g, 0.10 mmol) and 0.5M ammonia in dioxane (0.9 mL, 0.45 mmol). The reaction mixture was stirred at room temperature overnight. Further 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (0.007 g, 0.038 mmol) and ammonia in dioxane (0.57 mL, 0.29 mmol) were added and the reaction stirred for 3 hours at room temperature. The solvent was evaporated in vacuo and the residue purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(phenylamino)oxazole-4-carboxamide (0.006 g, 0.019 mmol, 20%) as a white solid. 1H NMR (DMSO) δ 7.03 (1H, dd), 7.35 (4H, m), 7.38 (2H, br. s), 7.43 (2H, m), 7.64 (1H, m), 9.34 (1H, br. s). LCMS (2) Rt 2.87 min; m/z (ES+) 338 (M+Na), 299 (M-NH2).

Workup

  1. stirringthe reaction stirred for 3 hours at room temperature
  2. customThe solvent was evaporated in vacuo
  3. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-84a05d116251431893f53a141ec8a7bd
Source dataset
uspto-grants-2013_02
Patent number
US08378095B2

Reaction notes

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