Methyl iodide → HCID 90403033, compound

HRID 2200649Notes

Reaction equation

HRID 2200649 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][CH:12]([OH:46])[CH2:13][N:14]1[C:22](=[O:23])[C:21]2[N:20]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C:19]([O:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([O:39][C:40]([F:43])([F:42])[F:41])[CH:34]=3)=[N:18][C:17]=2[N:16]([CH3:44])[C:15]1=[O:45])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].I[CH3:48]>C1COCC1>[Si:3]([O:10][CH2:11][CH:12]([O:46][CH3:48])[CH2:13][N:14]1[C:22](=[O:23])[C:21]2[N:20]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)[C:19]([O:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([O:39][C:40]([F:41])([F:43])[F:42])[CH:34]=3)=[N:18][C:17]=2[N:16]([CH3:44])[C:15]1=[O:45])([C:6]([CH3:7])([CH3:8])[CH3:9])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 90403361HCID 90403361, compound

Product 1

HCID 90403033HCID 90403033, compoundYield 118%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a slurry of sodium hydride (240 mg, 9.6 mmol) in anhydrous THF (10 ml) was added dropwise a solution of 1-(3-(tert-butyldimethylsilyloxy)-2-hydroxypropyl)-7-(4-chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (124 mg, 0.19 mmol) in THF (3 mL) at 0° C. under nitrogen. The reaction was stirred at 0° C. for 10 minutes. Then iodomethane (1.2 ml, 19.4 mmol) was added dropwise and the resulting mixture was allowed to warm from 0° C. to room temperature over 2 h. The mixture was quenched with ice-water (5 mL). The mixture was concentrated, diluted with ethyl acetate and water, and the organic layer was separated. The organic layer was dried over sodium sulfate, filtered and concentrated to give crude product (150 mg, 100% yield) as yellow oil. LCMS MH+ 669.

Workup

  1. temperatureto warm from 0° C. to room temperature over 2 h
  2. customThe mixture was quenched with ice-water (5 mL)
  3. concentrationThe mixture was concentrated
  4. additiondiluted with ethyl acetate and water
  5. customthe organic layer was separated
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-bc0ac814ff2a4756bd016669dcb08014
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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