Ammonia → HCID 25119994, compound

HRID 714934Notes

Reaction equation

HRID 714934 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]([C:22]([OH:24])=O)=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1.O.OC1C2N=N[NH:32]C=2C=CC=1.N.O1CCOCC1.CN(C)CCCN=C=NCC>CN(C=O)C>[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]([C:22]([NH2:32])=[O:24])=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1

Participants

7

Reactant 5

HCID 222Ammonia2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 312751,4-Dioxane2×HCID 59587418HCID 59587418, compoundHCID 178526939HCID 178526939, compound2×

Product 1

HCID 25119994HCID 25119994, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2,6-difluorophenyl)-4-(4-methoxyphenyl)oxazole-5-carboxylic acid (0.026 g, 0.08 mmol) and hydroxybenzotriazole monohydrate (0.012 g, 0.08 mmol) in DMF (3 mL) was added 0.5M ammonia in dioxane (0.471 mL, 0.24 mmol) and the reaction mixture stirred at room temperature for 10 minutes. 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (0.015 g, 0.08 mmol) was then added and the resulting reaction mixture stirred at room temperature overnight. After a further addition of hydroxybenzotriazole monohydrate (0.008 g, 0.05 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (0.010 g, 0.05 mmol) and 0.5M ammonia in dioxane (0.315 mL, 0.1116 mmol) the reaction mixture was stirred at room temperature for 4 hours. The solvent was evaporated in vacuo, and the residue was partitioned between DCM (10 mL) and water (10 mL). The organic phase was washed with water and brine, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-4-(4-methoxyphenyl)oxazole-5-carboxamide (0.018 g, 0.05 mmol, 69%) as a white solid. 1H NMR (CD3OD) δ 3.88 (3H, s), 7.03 (2H, d), 7.25 (2H, t), 7.68 (1H, m), 8.21 (2H, d). LCMS (2) Rt: 2.80; m/z (ES+) 331.

Workup

  1. customthe resulting reaction mixture
  2. stirringstirred at room temperature overnight
  3. stirringwas stirred at room temperature for 4 hours
  4. customThe solvent was evaporated in vacuo
  5. customthe residue was partitioned between DCM (10 mL) and water (10 mL)
  6. washThe organic phase was washed with water and brine
  7. dry with materialdried over MgSO4
  8. customthe solvent removed in vacuo
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-a7ed9abd2e0943d58a769b2045953aa1
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

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