Pyridine → N-(2-bromo-4-methyl-phenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamide

HRID 1465164Notes

Reaction equation

HRID 1465164 reaction equation
[F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH:11]([C:13]([OH:15])=O)[CH2:10][NH:9][C:8]=2[CH:16]=1.[Br:19][C:20]1[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:21]=1[NH2:22].N1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC1CCCO1>[Br:19][C:20]1[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:21]=1[NH:22][C:13]([CH:11]1[O:12][C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:18])[F:17])=[CH:16][C:8]=2[NH:9][CH2:10]1)=[O:15]

Participants

6

Reactant 4

HCID 1049PyridineHCID 114222-Bromo-4-methylanilineHCID 111923Propylphosphonic anhydrideHCID 593949626-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid

Product 1

HCID 59394939N-(2-bromo-4-methyl-phenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

6-(Trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (600 mg, 2.28 mmol) and 2-bromo-4-methyl-aniline (424 mg, 286 μL, 2.28 mmol) were dissolved in 2-methyltetrahydrofuran (7 mL) and pyridine (461 μL, 5.70 mmol). T3P (2902 mg, 2.7 mL of 50% w/w solution, 4.56 mmol) was added and the reaction was stirred for 30 min at room temperature. Purification by silica gel chromatography (10-100% ethyl acetate/hexanes) provided N-(2-bromo-4-methylphenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide (743 mg, 76% yield). LC/MS m/z 432.4 [M+H]+.

Workup

  1. customPurification by silica gel chromatography (10-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1cb2ec73b623405aafc794270f68c2dc
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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