Dimethylformamide → 4-Chloro-2,6-bis(trifluoromethyl)quinazoline

HRID 1896907Notes

Reaction equation

HRID 1896907 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[N:12]=[C:11](O)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[N:4]=1.CN(C=O)C.C(N(C(C)C)CC)(C)C.C(Cl)(=O)C([Cl:37])=O>C(Cl)Cl>[Cl:37][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[N:4]=[C:3]([C:2]([F:19])([F:18])[F:1])[N:12]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 178517785HCID 178517785, compound

Product 1

HCID 341762704-Chloro-2,6-bis(trifluoromethyl)quinazoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2,6-bis(trifluoromethyl)quinazolin-4-ol (200 mg, 0.666 mmol, prepared in the previous step), DMF (0.01 mL, 0.129 mmol) and diisopropylethylamine (0.17 mL, 0.986 mmol) suspended in dry DCM (10 mL) and treated dropwise with oxalyl chloride (0.11 mL, 1.26 mmol) under argon. After the addition, the reaction mixture was heated to reflux for 4 hours. After cooling to room temperature, the reaction was quenched by the cautious addition of potassium phosphate dibasic solution (20% w/w) and extracted with dichloromethane. The combined organic layers were washed with brine and dried over Na2SO4 and concentrated to yield the product as a white solid.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 4 hours
  4. customthe reaction was quenched by the cautious addition of potassium phosphate dibasic solution (20% w/w)
  5. extractionextracted with dichloromethane
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-47d9adc91e9a4a2aad645ec2536232d2
Source dataset
uspto-grants-2013_08
Patent number
US08518969B2

Reaction notes

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