Acetyl chloride → HCID 86687781, compound

HRID 1473696Notes

Reaction equation

HRID 1473696 reaction equation
C[O:2][C:3]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[O:23][CH3:24])[C:10]2[C:5](=[CH:6][C:7]([S:25]([NH:28][C:29]3[S:30][CH:31]=[CH:32][N:33]=3)(=[O:27])=[O:26])=[CH:8][CH:9]=2)[N:4]=1.C(Cl)(=O)C>CO>[NH4+:4].[OH-:2].[CH3:24][O:23][C:14]1[CH:15]=[C:16]([C:19]([F:22])([F:20])[F:21])[CH:17]=[CH:18][C:13]=1[C:11]1[C:10]2[C:5](=[CH:6][C:7]([S:25]([NH:28][C:29]3[S:30][CH:31]=[CH:32][N:33]=3)(=[O:26])=[O:27])=[CH:8][CH:9]=2)[NH:4][C:3](=[O:2])[N:12]=1

Participants

5

Reactant 2

HCID 6367Acetyl chloride2×HCID 86687743HCID 86687743, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 86687781HCID 86687781, compoundYield 151%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (Example 511; 0.075 g, 0.151 mmol) in 5 mL MeOH was treated with acetyl chloride (0.215 ml, 3.02 mmol) and was allowed to stir overnight at room temperature. An additional portion of acetyl chloride (0.215 ml, 3.02 mmol) was added, and the reaction mixture was heated to 100° C. for one hour. LC/MS showed mostly product, so the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18, 30μ, 55 g, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 4-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxo-N-(thiazol-2-yl)-1,2-dihydroquinazoline-7-sulfonamide (0.055 g, 0.114 mmol, 75% yield) as an off-white solid. 1H NMR (MeCN-d3) δ: 7.80 (s, 1H), 7.43-7.55 (m, 5H), 7.39 (d, J=8.4 Hz, 1H), 7.02 (d, J=4.7 Hz, 1H), 6.66 (d, J=4.7 Hz, 1H), 3.78 (s, 3H); (M+H)+=483.0.

Workup

  1. temperaturethe reaction mixture was heated to 100° C. for one hour
  2. concentrationso the reaction mixture was concentrated
  3. customPurification of the crude residue by reverse phase column chromatography [Puriflash

Sources & evidence

ORD record
ord-51f4032c7361416285fbb6ac9c90e80a
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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