Tetrahydrofuran → (8-chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)carbamic acid tert-butyl ester

HRID 729396Notes

Reaction equation

HRID 729396 reaction equation
C(O[C:6]([N:8]([C:10](=[O:24])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([F:18])=[C:13]([Cl:19])[C:12]=1[NH:20][CH:21]1[CH2:23][CH2:22]1)[NH2:9])=[O:7])(C)(C)C.[C:25](=[O:28])([O-])[O-:26].[K+].[K+].Cl[C:32](Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.O1[CH2:47][CH2:46][CH2:45]C1>C(OCC)(=O)C>[C:46]([O:26][C:25](=[O:28])[NH:9][N:8]1[C:10](=[O:24])[C:11]2[C:12](=[C:13]([Cl:19])[C:14]([F:18])=[C:15]([F:17])[CH:16]=2)[N:20]([CH:21]2[CH2:22][CH2:23]2)[C:6]1=[O:7])([CH3:45])([CH3:47])[CH3:32]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 94429TriphosgeneHCID 86591203(3-Chloro-2-cyclopropylamino-4,5-difluorobenzoyl)-hydrazinecarboxylic acid tert-butyl ester

Product 1

HCID 11440606(8-chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3-chloro-2-cyclopropylamino-4,5-difluorobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (Example 6c) (1.93 g, 5.34 mmol) in tetrahydrofuran (50 mL) is added potassium carbonate (3.69 g, 26.7 mol) and triphosgene (2.06 g, 6.95 mmol). The reaction mixture is refluxed for 90 minutes, cooled to room temperature, and diluted with ethyl acetate. The organic layer is washed with water and brine, then dried over MgSO4 and filtered. The filtrate is concentrated under vacuum and purified via flash column chromatography (1:2 ethyl acetate/hexanes) to afford the title compound (1.27 g). MS EI: m/z 386 (M+).

Workup

  1. temperatureThe reaction mixture is refluxed for 90 minutes
  2. washThe organic layer is washed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate is concentrated under vacuum
  6. custompurified via flash column chromatography (1:2 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ce02a5fe805948b9b90fc0ad116a6e5f
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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