1-Methylimidazole → HCID 86687743, compound

HRID 1473667Notes

Reaction equation

HRID 1473667 reaction equation
[CH3:1][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](Cl)(=[O:27])=[O:26])=[CH:8][CH:9]=2)[N:4]=1.[S:29]1[CH:33]=[CH:32][N:31]=[C:30]1[NH2:34].CN1C=CN=C1>CC#N.CO>[NH4+:4].[OH-:2].[CH3:1][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:34][C:30]3[S:29][CH:33]=[CH:32][N:31]=3)(=[O:27])=[O:26])=[CH:8][CH:9]=2)[N:4]=1

Participants

7

Reactant 3

HCID 13901-MethylimidazoleHCID 21552-AminothiazoleHCID 86687744HCID 86687744, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 86687743HCID 86687743, compoundYield 123.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazoline-7-sulfonyl chloride (0.141 g, 0.326 mmol) and thiazol-2-amine (0.163 g, 1.629 mmol) in 5 mL MeCN was flooded with argon, and was treated with 1-methylimidazole (0.026 ml, 0.326 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 2-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (0.100 g, 0.201 mmol, 61.8% yield) as an off-white solid. 1H NMR (MeCN-d3) δ: 8.26 (d, J=1.7 Hz, 1H), 7.70-7.76 (m, 1H), 7.63-7.68 (m, 1H), 7.54-7.57 (m, 1H), 7.42-7.48 (m, 2H), 7.01 (d, J=4.7 Hz, 1H), 6.64 (d, J=4.7 Hz, 1H), 4.13 (s, 3H), 3.76 (s, 3H). m/z (M+H)+=497.0.

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-7f3ceaa382ad463b9d495bbf3f70192c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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