Methyl iodide → HCID 86615239, compound

HRID 2244381Notes

Reaction equation

HRID 2244381 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:33][C:34](=[O:39])[C:35]([F:38])([F:37])[F:36])=[C:6]([CH:32]=1)[C:7]([N:9]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:31][CH2:30]2)=[CH:25][CH:24]=1)[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)=[O:8].[CH3:40]N1C(=O)N(C)CCC1.[H-].[Na+].CI>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:33]([CH3:40])[C:34](=[O:39])[C:35]([F:36])([F:37])[F:38])=[C:6]([CH:32]=1)[C:7]([N:9]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:30][CH2:31]2)=[CH:25][CH:24]=1)[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)=[O:8]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 86615240HCID 86615240, compound

Product 1

HCID 86615239HCID 86615239, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

50 mg of 5-chloro-N-(4-cyclopropyl-benzyl)-2-(2,2,2-trifluoro-acetylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide (0.09 mmol) were dissolved in 1 ml DMF and 0.1 ml DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2-pyridinon) under argon and cooled down to 0° C. 6 mg of sodium hydride (55% dispersion in oil, 0.135 mmol) were then added and after 15 min stirring at RT the reaction mixture was again cooled down to 0° C. 0.008 ml of methyl iodide (0.135 mmol) were added and after 4 h stirring at RT a second portion of the same amount was added. After 20 hours stirring at RT the reaction mixture was diluted with ethyl acetate and washed with water and brine. The aqueous phases were reextracted with ethyl acetate, and the combined organic phases were dried over magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane/EtOAc 9:1) to give 36 mg (70%) 5-chloro-N-(4-cyclopropyl-benzyl)-2-[methyl-(2,2,2-trifluoro-acetyl)-amino]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide as a colorless viscous oil. MS (ISP) 583.2 (M+H)+.

Workup

  1. temperaturewas again cooled down to 0° C
  2. stirringstirring at RT a second portion of the same amount
  3. additionwas added
  4. stirringAfter 20 hours stirring at RT the reaction mixture
  5. washwashed with water and brine
  6. dry with materialthe combined organic phases were dried over magnesium sulfate
  7. filtrationfiltered off
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica gel; heptane/EtOAc 9:1)

Sources & evidence

ORD record
ord-eb9c7577798649668b2402e64539ba5a
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

Loading…