Pyridine → 4-Bromo-2-cyclopentyl-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate

HRID 471996Notes

Reaction equation

HRID 471996 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.[C:19](=[O:36])([O:34][CH3:35])[O:20][C:21]1[CH:26]=[C:25]([NH2:27])[C:24]([Br:28])=[CH:23][C:22]=1[CH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.N1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC1CCCO1>[C:19](=[O:36])([O:34][CH3:35])[O:20][C:21]1[CH:26]=[C:25]([NH:27][C:13]([CH:11]2[O:12][C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:18])[F:17])=[CH:16][C:8]=3[NH:9][CH2:10]2)=[O:15])[C:24]([Br:28])=[CH:23][C:22]=1[CH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 111923Propylphosphonic anhydrideHCID 593949626-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acidHCID 59394974HCID 59394974, compound

Product 1

HCID 593949824-Bromo-2-cyclopentyl-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonateYield 77.1%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

6-(Trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (490 mg, 1.86 mmol) and (5-amino-4-bromo-2-cyclopentyl-phenyl) methyl carbonate (585 mg, 1.86 mmol) were dissolved in 2-methyltetrahydrofuran (13 mL). Pyridine (376 μL, 4.65 mmol) and T3P (2960 mg, 2.8 mL of 50% w/w solution, 4.66 mmol) were added and the reaction was stirred for 1 h at room temperature. Purification by silica gel chromatography (10-75% ethyl acetate/hexanes) yielded 4-bromo-2-cyclopentyl-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate (802 mg, 77% yield). LC/MS m/z 560.2 [M+H]+.

Workup

  1. customPurification by silica gel chromatography (10-75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-58a0f858f2774f0aa23060c3f8f7bc33
Source dataset
uspto-grants-2014_01
Patent number
US08633189B2

Reaction notes

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