Methyl iodide → HCID 89761344, compound

HRID 528535Notes

Reaction equation

HRID 528535 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=3[O:40][CH3:41])[C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[NH:15][CH2:14][CH2:13]1.[H-].[Na+].I[CH3:45]>CN(C=O)C.O.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:9])[F:11])[CH:5]=[CH:4][C:3]=1[N:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=3[O:40][CH3:41])[C:26]3[S:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[N:15]([CH3:45])[CH2:14][CH2:13]1

Participants

7

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 89761773HCID 89761773, compound2×

Product 1

HCID 89761344HCID 89761344, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (INTERMEDIATE V, 0.045 g, 0.072 mmol) in DMF (0.719 mL) was treated with sodium hydride (4.31 mg, 0.108 mmol) to afford a dark brown solution. Iodomethane (6.74 μL, 0.108 mmol) was added dropwise to give a light-yellow solution. The reaction was stirred for 40 minutes. Additional iodomethane (6.74 μL, 0.108 mmol) was added and the reaction was heated to 70° C. and stirred for one hour. The mixture was diluted with water and a small amount of brine (to break up an emulsion) then extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The material was purified via silica gel chromatography (12 g column, gradient elution 0 to 50% EtOAc:Heptane) to afford 1-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-4-methyl-N-(1,2,4-thiadiazol-5-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide as a white solid. m/z (ESI) 639.8 (M+H)+.

Workup

  1. customto afford a dark brown solution
  2. customto give a light-yellow solution
  3. stirringstirred for one hour
  4. extractionthen extracted with EtOAc (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via silica gel chromatography (12 g column, gradient elution 0 to 50% EtOAc:Heptane)

Sources & evidence

ORD record
ord-bafd690917974cf19f2f960f8d4aa4f0
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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