Methyl iodide → 2-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

HRID 220722

Reaction equation

HRID 220722 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:6][C:7](=[O:20])[C:8]([F:19])([F:18])[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[H-].[Na+].[CH3:23]I>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:23])[C:7](=[O:20])[C:8]([F:18])([F:19])[CH2:9][N:10]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17]3)[C:11]=2[N:12]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 579556112-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Product 1

HCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (550 mg, 1.82 mmol) was dissolved in DMA (10 mL) and cooled in an ice bath. Sodium hydride (80 mg of 60% in mineral oil, 2 mmol) was added slowly and left to stir for 10 minutes. Methyl iodide (0.125 mL, 2 mmol) was then added and the reaction mixture was warmed up to room temperature. After 30 minutes the reaction was deemed complete by LCMS, poured into ice water, the solution extracted with EtOAc. The organic layer washed with brine and water, dried over MgSO4, and concentrated to give 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one as a brown residue which was used directly for next step. [M+H] calc'd for C13H15ClF2N4O, 317; found 317.

Workup

  1. temperaturecooled in an ice bath
  2. waitleft
  3. waitAfter 30 minutes the reaction was deemed complete by LCMS
  4. extractionthe solution extracted with EtOAc
  5. washThe organic layer washed with brine and water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-07544f1ddff94409b3ace1e857f185ce
Source dataset
uspto-grants-2012_06
Patent number
US08202990B2

Linked notes

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