Diisopropylethylamine → n-(6-Oxazol-5-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl)-methanesulfonamide

HRID 906633Notes

Reaction equation

HRID 906633 reaction equation
CO[C:3](=[O:20])[C:4]1[CH:9]=[C:8]([C:10]2[O:14][CH:13]=[N:12][CH:11]=2)[C:7]([C:15]([F:18])([F:17])[F:16])=[CH:6][C:5]=1[NH2:19].ClC([O:24][C:25]1C=CC(Cl)=CC=1)=O.[CH3:32][S:33]([NH:36][NH2:37])(=[O:35])=[O:34].CCN(C(C)C)C(C)C>O1CCOCC1>[O:14]1[C:10]([C:8]2[CH:9]=[C:4]3[C:5](=[CH:6][C:7]=2[C:15]([F:16])([F:17])[F:18])[NH:19][C:25](=[O:24])[N:37]([NH:36][S:33]([CH3:32])(=[O:35])=[O:34])[C:3]3=[O:20])=[CH:11][N:12]=[CH:13]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1390594-Chlorophenyl chloroformateHCID 269268MethanesulfonohydrazideHCID 119646012-Amino-5-oxazol-5-yl-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 11964602n-(6-Oxazol-5-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl)-methanesulfonamideYield 19.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-5-oxazol-5-yl-4-trifluoromethyl-benzoic acid methyl ester (248 mg, 0.866 mmol) and 4-chlorophenyl chloroformate (121 μL, 0.886 mmol) in dioxane (4 mL) was heated to 80° C. for 1 h. The reaction mixture was concentrated in vacuo. The crude residue was dissolved in dioxane (4 mL) and treated with CH3SO2NHNH2 (191 mg, 1.732 mmol) and i-Pr2NEt (454 μL, 2.60 mmol). After heating at 80° C. for 1 h, the reaction mixture was concentrated in vacuo. The residue was purified by two successive flash chromatographies (70 g of silica gel, 2% MeOH in DCM), then (20 g silica gel, DCM→MeOH in DCM (1% to 3%)) to give the title compound (65 mg) as an off-white powder. This solid was further purified by sonication in DCM to provide 24 mg of pure product. The filtrate was concentrated in vacuo and sonicated in Et2O to give a further 27.8 mg of title product, for a total of 51.8 mg (15%) of the title compound as an off-white powder. API-ES: m/z 408.0 [M+NH4]+, rt 2.89 min.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe crude residue was dissolved in dioxane (4 mL)
  3. temperatureAfter heating at 80° C. for 1 h
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customThe residue was purified by two successive flash chromatographies (70 g of silica gel, 2% MeOH in DCM)

Sources & evidence

ORD record
ord-08bafa483699492c81f56e4a5f84b891
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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