Methyl iodide → HCID 67410226, compound

HRID 1897452Notes

Reaction equation

HRID 1897452 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18](=[O:48])[N:19]([CH2:29][C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[O:37][C:38]2[CH:39]=[C:40]3[C:44](=[CH:45][CH:46]=2)[N:43]([CH3:47])[N:42]=[CH:41]3)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:51]I>CN(C=O)C>[C:1]([C:5]1[CH:6]=[C:7]([N:17]([CH3:51])[C:18]([N:19]([CH2:29][C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[O:37][C:38]2[CH:39]=[C:40]3[C:44](=[CH:45][CH:46]=2)[N:43]([CH3:47])[N:42]=[CH:41]3)[CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)=[O:48])[N:8]([C:10]2[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67413349HCID 67413349, compound

Product 1

HCID 67410226HCID 67410226, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Intermediate (30t) (150 mg, 0.23 mmol) was dissolved in DMF (2 mL) and cooled to 0° C. Sodium hydride (60% in oil, 14 mg, 0.36 mmol) and methyl iodide (73.8 μL, 168 mg, 1.19 mmol) were added to the solution at 0° C. and the reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was quenched by addition of 5 mL of water at 0° C., and then extracted three times with 50 mL of Et2O. The combined organic layer was washed with 5 mL of water twice and with brine once, dried over MgSO4, filtered and evaporated under reduced pressure. The residue was purified on silica gel with EtOAc/hexane (1:2) to obtain compound (31t) as a pale yellow amorphous (134 mg, 87% yield). 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.37 (d, J=8.6 Hz, 2H), 7.28 (d, J=9.4 Hz, 1H), 7.15-7.02 (m, 2H), 7.00-6.81 (m, 6H), 6.80-6.60 (m, 3H), 5.85 (s, 1H), 4.21 (s, 2H), 4.20 (s, 2H), 4.05 (s, 3H), 3.76 (s, 3H), 2.98 (s, 3H), 2.29 (s, 3H), 1.23 (s, 9H) ppm.

Workup

  1. customThe reaction mixture was quenched by addition of 5 mL of water at 0° C.
  2. extractionextracted three times with 50 mL of Et2O
  3. washThe combined organic layer was washed with 5 mL of water twice
  4. dry with materialwith brine once, dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified on silica gel with EtOAc/hexane (1:2)

Sources & evidence

ORD record
ord-99585059711e4256b63c29151a2e0338
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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