1-Methylimidazole → 4-[2-Methoxy-4-(trifluoromethyl)phenyl]-N-4-pyrimidinyl-7-quinazolinesulfonamide

HRID 1473482Notes

Reaction equation

HRID 1473482 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.C[Si](CCOCCl)(C)C.[CH3:17][O:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[C:29]1[C:38]2[C:33](=[CH:34][C:35]([S:39](Cl)(=[O:41])=[O:40])=[CH:36][CH:37]=2)[N:32]=[CH:31][N:30]=1.CN1C=CN=C1>CC#N>[CH3:17][O:18][C:19]1[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][C:20]=1[C:29]1[C:38]2[C:33](=[CH:34][C:35]([S:39]([NH:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)(=[O:41])=[O:40])=[CH:36][CH:37]=2)[N:32]=[CH:31][N:30]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 689584-AminopyrimidineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 86687533HCID 86687533, compound

Product 1

HCID 866875344-[2-Methoxy-4-(trifluoromethyl)phenyl]-N-4-pyrimidinyl-7-quinazolinesulfonamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
110 °C

Procedure

A solution of pyrimidin-4-amine (0.029 g, 0.300 mmol) in 3 mL of MeCN was treated with SEM-Cl (0.053 ml, 0.300 mmol), and the reaction mixture was allowed to stir for one hour. 4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazoline-7-sulfonyl chloride (Intermediate DDDD; 0.110 g, 0.273 mmol) was added as a solution in 3 mL of MeCN, followed by 1-methylimidazole (0.054 ml, 0.546 mmol). After stirring at room temperature for an additional hour, the reaction mixture was concentrated and then dissolved in 1 mL of THF. 4N HCl dioxanes (1.024 ml, 4.10 mmol) was added, and the reaction mixture was heated to 110° C. for one hour. The reaction mixture was concentrated and purification of the crude residue by reverse phase column chromatography [C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielded 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide. 1H NMR (acetonitrile-d3) δ ppm: 9.44 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.18 (br. s., 1H), 8.03 (d, J=8.8 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.58 (d, J=7.4 Hz, 1H), 7.43-7.51 (m, 2H), 7.07 (br. s., 1H), 3.75 (s, 3H). m/z (ESI) 462.0 (M+H)+

Workup

  1. stirringAfter stirring at room temperature for an additional hour
  2. concentrationthe reaction mixture was concentrated
  3. dissolutiondissolved in 1 mL of THF
  4. concentrationThe reaction mixture was concentrated
  5. custompurification of the crude residue by reverse phase column chromatography [C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-7483ce070b434702ad6909c8c52cf0d0
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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