Methyl iodide → (Rac)-2-chloro-9-cyclobutyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2111379Notes

Reaction equation

HRID 2111379 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH:9]([CH3:13])[CH2:8][N:7]([CH:14]3[CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:18]=1.I[CH3:20].[H-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:20])[C:10](=[O:12])[CH:9]([CH3:13])[CH2:8][N:7]([CH:14]3[CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:18]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 87555122HCID 87555122, compound

Product 1

HCID 87618676(Rac)-2-chloro-9-cyclobutyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.94 g (0.00352 mole) of (rac)-2-chloro-9-cyclobutyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-52), 0.33 mL (0.00529 mole) of iodomethane and 15 mL of N,N-dimethylformamide at 0 degrees, was added 0.21 g (0.00529 mole) of 60% oil dispersion of sodium hydride. The mixture was stirred at 0 degrees for 2 hours and then partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with hexanes-ethyl acetate (100:0-60:40) to give 0.88 g of (rac)-2-chloro-9-cyclobutyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-52) as white powder. HRMS (ES+) m/z Calcd for C13H17CLN4O2+H [(M+H)+]: 281.1164. Found: 281.1163.

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. washThe combined organic phases were washed successively with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with hexanes-ethyl acetate (100:0-60:40)

Sources & evidence

ORD record
ord-971888e1a5374e8fbc0aff9857c37312
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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