2-Chlorobenzoyl chloride → N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)(2-pyridyl)](2-chlorophenyl)carboxamide

HRID 2272199Notes

Reaction equation

HRID 2272199 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([CH3:18])[C:9]([C:11]3[CH:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=3)=[CH:10][C:5]=2[O:4][N:3]=1.[Cl:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][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>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([CH3:18])[C:9]([C:11]3[CH:12]=[CH:13][C:14]([NH:17][C:22]([C:21]4[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=4[Cl:19])=[O:23])=[N:15][CH:16]=3)=[CH:10][C:5]=2[O:4][N:3]=1

Participants

6

Reactant 4

HCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 23716255Sodium bicarbonate methylene chlorideHCID 584869675-(3,5-Dimethylbenzo[d]isoxazol-6-yl)-2-pyridylamine

Product 1

HCID 58486774N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)(2-pyridyl)](2-chlorophenyl)carboxamideYield 75.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(3,5-dimethylbenzo[d]isoxazol-6-yl)-2-pyridylamine (105) (14.5 mg, 0.06 mmol) in 1 ml DCM was added 2-chlorobenzoyl chloride (16 μl, 0.12 mmol) followed by addition of DIEA (63 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 (120 μl) at r.t. for 1 h before worked up with EA/aq. NaHCO3. Silica gel flash chromatography furnished N-[5-(3,5-dimethylbenzo[d]isoxazol-6-yl)(2-pyridyl)](2-chlorophenyl)carboxamide (106) (17.1 mg, yield: 75.4%, purity>95%) as off-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 (120 μl) at r.t. for 1 h

Sources & evidence

ORD record
ord-4bc016afcaf6413aa2b967261f7c7366
Source dataset
uspto-grants-2015_09
Patent number
US09120751B2

Reaction notes

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