Water → trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline

HRID 1498814Notes

Reaction equation

HRID 1498814 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][C:10]1[N:14]=[C:13]([CH3:15])[N:12]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18](/[CH:23]=[CH:24]/[C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]=3)[CH:17]=2)[N:11]=1.O>CS(C)=O>[CH3:9][C:10]1[N:14]=[C:13]([CH3:15])[N:12]([C:16]2[N:21]=[C:20]([CH3:22])[N:19]=[C:18]([C@@H:23]3[CH2:2][C@H:24]3[C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]=3)[CH:17]=2)[N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 86732074(E)-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)vinyl)quinoline

Product 1

HCID 86732075trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of trimethylsulfoxonium iodide (59.0 mg, 0.268 mmol, 1.3 eq.) in anhydrous DMSO (1.5 mL) was added sodium hydride (5.4 mg, 0.227 mmol, 1.1 eq.) and the reaction was heated to 50° C. for 30 minutes. The reaction was then cooled to room temperature and a solution of (E)-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)vinyl)quinoline (1-4) (70.0 mg, 0.205 mmol, 1.0 eq.) in DMSO (1.5 mL) was added. The reaction was stirred at room temperature for 1 hour, poured into water (5.0 mL) and extracted using ethyl acetate (3×5.0 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes) to afford trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)quinoline (1-5) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.03 (br d, 1H, J=8.5 Hz), 7.98 (br d, 1H, J=8.4 Hz), 7.75 (br dd, 1H, J=8.0, 1.0 Hz), 7.67 (ddd, 1H, J=8.5, 7.0, 1.5 Hz), 7.60 (br s, 1H), 7.46 (ddd, 1H, J=8.0, 7.0, 1.0 Hz), 7.33 (d, 1H, J=8.5 Hz), 2.96-2.83 (m, 2H), 2.89 (s, 3H), 2.68 (s, 3H), 2.06-1.94 (m, 2H). LRMS m/z (M+H+) 357 found, 357 required. m.p. 140-141° C.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. extractionextracted
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by silica gel column chromatography (10-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9265f5bc4bf34e9b8c63508b5a53a7a1
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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