Methyl iodide → HCID 86719522, compound

HRID 1772282Notes

Reaction equation

HRID 1772282 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][CH:13]([O:16][CH2:17][C:18]([N:20]3[CH2:25][CH2:24][N:23]([C:26]4[CH:35]=[CH:34][C:33]5[C:28](=[CH:29][CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[CH:32]=5)[N:27]=4)[CH2:22][CH2:21]3)=[O:19])[CH2:12][CH2:11]2)=[CH:5][C:4]=1[C:40]([F:43])([F:42])[F:41])#[N:2].[H-].[Na+].I[CH3:47]>C1COCC1.O>[CH3:47][N:9]([C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:40]([F:42])([F:43])[F:41])[CH:5]=1)[CH:10]1[CH2:15][CH2:14][CH:13]([O:16][CH2:17][C:18]([N:20]2[CH2:21][CH2:22][N:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[C:31]([C:36]([F:37])([F:38])[F:39])[CH:32]=4)[N:27]=3)[CH2:24][CH2:25]2)=[O:19])[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86719523HCID 86719523, compound

Product 1

HCID 86719522HCID 86719522, compoundYield 100.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[(4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]-cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]ethan-1-one (100 mg, 0.16 mmol) in THF (3 ml) was added sodium hydride (25 mg, 0.63 mmol, 3.9 eq.) and the mixture was stirred for 30 minutes. The mixture was then treated with iodomethane (100 mg, 0.7 mmol, 4 eq.) and stirred for 5 days. The resulting mixture was diluted with water (30 ml), and extracted with ethyl acetate (30 mL). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give a residue from which the product was purified by silica gel column flash chromatography eluting with ethyl acetate/heptanes to afford 2-[(4-[methyl[4-cyano-3-(trifluoromethyl)phenyl]-amino]-cyclohexyl)oxy]-1-[4-[6-(trifluoromethyl)quinolin-2-yl)piperazin-1-yl]ethan-1-one as a yellow solid (100 mg, 98%). (CI, m/z): [M+H]+ 620; 1H NMR (400 MHz, DMSO-d6): δ 8.24 (d, J=9.3 Hz, 1H), 8.17 (s, 1H), 7.76 (d, J=8.7 Hz, 2H), 7.70 (d, J=8.7 Hz, 1H), 7.40 (d, J=9.3 Hz, 1H), 7.13-7.07 (m, 2H), 4.23 (s, 2H), 3.94-3.76 (m, 5H), 3.63-3.57 (m, 4H), 3.41-3.32 (m, 1H), 2.85 (s, 3H), 2.14-2.05 (m, 2H), 1.69-1.57 (m, 4H), 1.50-1.38 (m, 2H).

Workup

  1. stirringstirred for 5 days
  2. extractionextracted with ethyl acetate (30 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give a residue from which the product
  9. customwas purified by silica gel column flash chromatography
  10. washeluting with ethyl acetate/heptanes

Sources & evidence

ORD record
ord-b9ba0734b10c4cd2bc9f1c7cb4a89ff8
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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