Water → HCID 67353582, compound

HRID 75851Notes

Reaction equation

HRID 75851 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([C:24]([NH:26][CH:27]([CH:32]([CH3:34])[CH3:33])[C:28]([O:30][CH3:31])=[O:29])=[O:25])[O:21][N:20]=2)=[CH:15][CH:14]=1.[OH2:35].CCO[C:39]([CH3:41])=[O:40]>C(Cl)(=O)C(Cl)=O>[CH3:33][CH:32]([CH3:34])[CH:27]([NH:26][C:24]([C:22]1[O:21][N:20]=[C:19]([C:16]2[CH:17]=[CH:18][C:13]([NH:12][C:39](=[O:40])[C:41](=[O:35])[NH:6][C:5]3[CH:7]=[CH:8][CH:9]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=3)=[CH:14][CH:15]=2)[CH:23]=1)=[O:25])[C:28]([O:30][CH3:31])=[O:29]

Participants

6

Reactant 4

HCID 962WaterHCID 73753-(Trifluoromethyl)anilineHCID 8857Ethyl AcetateHCID 67352790Methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate

Product 1

HCID 67353582HCID 67353582, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 65578Oxalyl chlorideSolvent

Procedure

To 3-(trifluoromethyl)aniline (0.117 ml), methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate (300 mg, example 151, step 3) in EtOAc (6 ml), oxalyl chloride was added and stirred at RT for 3 hours. To this water was added and organic layer was collected and dried over Na2SO4 and concentrated to obtain brown solid which was purified by column chromatography (silica gel, EtOAc—CHCl3 to obtain pale brown solid which was crystallized from DCM-Petroleum ether to yield 150 mg (29%) of the title compound as off white solid. MS (ES+): m/z 533 (M+1); 1HNMR (DMSO-d6; 300 MHz): δ 11.24 (s, 1H), 11.14 (s, 1H), 9.25 (d, 1H), 8.35 (dd, 1H), 8.16 (dd, 1H), 8.06 (d, 2H), 7.96 (d, 2H), 7.72 (s, 1H), 7.64 (m, 1H), 7.54 (dd, 1H), 4.31 (m, 1H), 3.68 (s, 3H), 2.23 (m, 1H), 0.97 (d, 6H).

Workup

  1. customorganic layer was collected
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto obtain brown solid which
  5. customwas purified by column chromatography (silica gel, EtOAc—CHCl3
  6. customto obtain pale brown solid which
  7. customwas crystallized from DCM-Petroleum ether

Sources & evidence

ORD record
ord-574ec6e76d6248ebb9703b9165ef265e
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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