Diisopropylethylamine → (2,6-difluorophenyl)-N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)pyrazin-2-yl]carboxamide

HRID 874630Notes

Reaction equation

HRID 874630 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([CH3:18])[C:9]([C:11]3[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=3)=[CH:10][C:5]=2[O:4][N:3]=1.[F:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:21]=1[C:22](Cl)=[O:23].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].C(Cl)Cl>C(Cl)Cl>[F:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:21]=1[C:22]([NH:17][C:14]1[CH:13]=[N:12][C:11]([C:9]2[C:8]([CH3:18])=[CH:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH:10]=2)=[CH:16][N:15]=1)=[O:23]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 23716255Sodium bicarbonate methylene chlorideHCID 584866795-(3,5-Dimethylbenz[d]isoxazol-6-yl)pyrazine-2-ylamine

Product 1

HCID 58487343(2,6-difluorophenyl)-N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)pyrazin-2-yl]carboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(3,5-dimethylbenz[d]isoxazol-6-yl)pyrazine-2-ylamine (109) (7.5 mg, 0.03 mmol) in 1 ml DCM was added 2,6-difluorobenzoyl chloride (11 μl, 0.09 mmol) followed by addition of DIEA (47 μl). The resulting solution was stirred at r.t. for 2 h. The reaction mixture was worked up with aq. NaHCO3/DCM. DCM phase was washed with brine, concentrated to dryness. The residue was dissolved in 2 ml THF/MeOH/H2O (5:4:1) and stirred with 1N NaOH (90 μl) at r.t. for 1 h before worked up with EA/aq. NaHCO3. Silica gel flash chromatography furnished 7.3 mg (yield: 63.8%, purity>95%) (2,6-difluorophenyl)-N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)pyrazin-2-yl]carboxamide (110) as white solid.

Workup

  1. washDCM phase was washed with brine
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in 2 ml THF/MeOH/H2O (5:4:1)
  4. stirringstirred with 1N NaOH (90 μl) at r.t. for 1 h

Sources & evidence

ORD record
ord-2d2ccf5081d3401285843ec1fdcf2629
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

Loading…