Hydrogen Peroxide → HCID 66763374, compound

HRID 578659Notes

Reaction equation

HRID 578659 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[C:17]([C:19]#[N:20])[CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=[O:34].[K+].[K+].OO>CS(C)=O.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[C:17]([C:19]([NH2:20])=[O:34])[CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2[NH:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:27][CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 66762993HCID 66762993, compound

Product 1

HCID 66763374HCID 66763374, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of the 6-Benzyloxy-4-(4-trifluoromethyl-benzylamino)-quinazoline-8-carbonitrile (380 mg, 1 eq) in DMSO (20 mL) was added 10 wt % aqueous K2CO3 (6.68 mL, 5 eq) followed by 33% H2O2 (790 □L, 8 eq) at room temperature. The resulting light suspension was stirred for 12 h at room temperature and then diluted with water (˜20-40 mL). A white precipitate formed that was collected by filtration (crop A). The filtrate was then extracted with ethyl acetate (3×25 mL) and the combined organic layers were dried over sodium sulfate, concentrated to an oil and columned (50 to 90% ethyl acetate/heptane) to afford an off-white solid (crop B). The two crops of carboxamide product (A+B, each ˜90% pure by HPLC) were then combined in a 20 mL vial and triturated with minimal dichloromethane followed by ether. Trituration afforded a white solid (342.6 mg, 86%) LCMS (ESI) 453 (M+H)

Workup

  1. customA white precipitate formed
  2. filtrationthat was collected by filtration (crop A)
  3. extractionThe filtrate was then extracted with ethyl acetate (3×25 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated to an oil
  6. customto afford an off-white solid (crop B)
  7. customtriturated with minimal dichloromethane

Sources & evidence

ORD record
ord-b70ac3fdc4864e2ca5eb54ca9a7b4005
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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