1-Methylimidazole → 1-(2-Methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-YL)phthalazine-6-sulfonamide

HRID 1473476Notes

Reaction equation

HRID 1473476 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].C[Si](CCOCCl)(C)C.[CH3:16][O:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[C:28]1[C:37]2[C:32](=[CH:33][C:34]([S:38](Cl)(=[O:40])=[O:39])=[CH:35][CH:36]=2)[CH:31]=[N:30][N:29]=1.CN1C=CN=C1>CC#N>[CH3:16][O:17][C:18]1[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][C:19]=1[C:28]1[C:37]2[C:32](=[CH:33][C:34]([S:38]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)(=[O:40])=[O:39])=[CH:35][CH:36]=2)[CH:31]=[N:30][N:29]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 21552-AminothiazoleHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 866874491-(2-Methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonyl chloride

Product 1

HCID 866875251-(2-Methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-YL)phthalazine-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of thiazol-2-amine (0.027 g, 0.273 mmol) in 3 mL of MeCN was treated with SEM-Cl (0.048 ml, 0.273 mmol), and the reaction mixture was allowed to stir for one hour. LC/MS showed mostly product, so 1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonyl chloride (Intermediate BBBB; 0.100 g, 0.248 mmol) was added as a solution in 3 mL of MeCN, followed by 1-methylimidazole (0.049 ml, 0.497 mmol). After stirring at room temperature for an additional hour, LC/MS showed mostly desired product. The reaction mixture was concentrated then dissolved in 4N HCl in dioxanes (1.862 ml, 7.45 mmol), and the reaction mixture was heated to 110° C. for 3 hours. The reaction mixture was concentrated and was purified by reverse phase column chromatography [C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] to yield 1-(2-methoxy-4-(trifluoromethyl)phenyl)-n-(thiazol-2-yl)phthalazine-6-sulfonamide. 1H NMR (acetonitrile-d3) δ ppm: 9.70 (s, 1H), 8.63 (s, 1H), 8.20 (d, J=8.7 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.62 (d, J=7.7 Hz, 1H), 7.45-7.53 (m, 2H), 7.02 (d, J=4.7 Hz, 1H), 6.65 (d, J=4.7 Hz, 1H), 3.75 (s, 3H). m/z (ESI) 467.0 (M+H)+

Workup

  1. stirringAfter stirring at room temperature for an additional hour

Sources & evidence

ORD record
ord-9369039a966044da86ff118efbd31736
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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