1-Methylimidazole → HCID 86687737, compound

HRID 1473662Notes

Reaction equation

HRID 1473662 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23](Cl)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[N:16]=[C:15]([CH3:27])[N:14]=1.[S:28]1[CH:32]=[CH:31][N:30]=[C:29]1[NH2:33].CN1C=CN=C1>CC#N.CO>[NH4+:14].[OH-:2].[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([NH:33][C:29]3[S:28][CH:32]=[CH:31][N:30]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[N:16]=[C:15]([CH3:27])[N:14]=1

Participants

7

Reactant 3

HCID 13901-MethylimidazoleHCID 21552-AminothiazoleHCID 86687738HCID 86687738, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 86687737HCID 86687737, compoundYield 132.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-2-methylquinazoline-7-sulfonyl chloride (Intermediate QQQQQ; 0.210 g, 0.504 mmol) and thiazol-2-amine (0.252 g, 2.52 mmol) in 5 mL MeCN was flooded with argon, and was treated with 1-methylimidazole (0.040 ml, 0.504 mmol). After stirring for 2 hours, 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-methyl-N-(thiazol-2-yl)quinazoline-7-sulfonamide (0.160 g, 0.333 mmol, 66.1% yield) as an off-white solid. 1H NMR (MeCN-d3) δ: 8.39 (d, J=1.7 Hz, 1H), 7.86 (dd, J=8.7, 1.8 Hz, 1H), 7.70 (d, J=8.7 Hz, 1H), 7.52-7.57 (m, 1H), 7.44-7.50 (m, 2H), 7.01 (d, J=4.7 Hz, 1H), 6.63 (d, J=4.7 Hz, 1H), 3.75 (s, 3H), 2.85 (s, 3H); (M+H)+=481.0.

Workup

  1. concentrationso the reaction mixture was concentrated
  2. customPurification of the crude residue by reverse phase column chromatography [Puriflash

Sources & evidence

ORD record
ord-859563e7c4e543a4a004e3845483aa03
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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