Methyl iodide → HCID 67431770, compound

HRID 410550Notes

Reaction equation

HRID 410550 reaction equation
[C:1]([O:5][C:6]([N:8]([C:33]1[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=1)[C:9]1[CH:10]=[C:11]([C:16]2[S:20][C:19]([C:21]3([OH:32])[CH2:26][CH2:25][CH:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:18][CH:17]=2)[CH:12]=[C:13]([CH3:15])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH3:44].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([C:33]1[N:38]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:36]=[CH:35][N:34]=1)[C:9]1[CH:10]=[C:11]([C:16]2[S:20][C:19]([C:21]3([O:32][CH3:44])[CH2:22][CH2:23][CH:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:25][CH2:26]3)=[N:18][CH:17]=2)[CH:12]=[C:13]([CH3:15])[CH:14]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 58456092HCID 58456092, compound

Product 1

HCID 67431770HCID 67431770, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 4-[5-(3-{(tert-butoxycarbonyl)[4-(trifluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxycyclohexanecarboxylate (0.148 g, 0.24 mmol) and DMF (1.2 mL) was added iodomethane (0.042 g, 0.29 mmol). The solution was cooled to 0° C. and then 60% sodium hydride in mineral oil (0.011 g, 0.27 mmol) was added and the reaction was allowed to warm up overnight. The next morning, iodomethane (1.14 g, 8.03 mmol) was added and the mixture was cooled to 0° C. Sodium hydride in mineral oil (60%, 0.011 g, 0.27 mmol) was added and the reaction was allowed to warm to room temperature. The reaction was complete after warming. The solution was cooled to 0° C. and carefully quenched with methanol and then water. The mixture was extracted with dichloromethane. The organic layer was washed three times with water, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography was used to yield ethyl 4-[5-(3-{(tert-butoxycarbonyl)[4-(trifluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-4-methoxycyclohexanecarboxylate. MS ESI: [M+H]+ m/z 621.2.

Workup

  1. temperatureto warm up overnight
  2. temperaturethe mixture was cooled to 0° C
  3. temperatureto warm to room temperature
  4. temperatureafter warming
  5. temperatureThe solution was cooled to 0° C.
  6. customcarefully quenched with methanol
  7. extractionThe mixture was extracted with dichloromethane
  8. washThe organic layer was washed three times with water
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-8d41f08776d94918a2773903ab95726f
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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