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 1881020Notes

Reaction equation

HRID 1881020 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C:9]([F:14])([F:13])[CH2:8][N:7]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:20]=1.[H-].[Na+].I[CH3:24]>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:24])[C:10](=[O:12])[C:9]([F:14])([F:13])[CH2:8][N:7]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:20]=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)-oneYield 93.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (100 g, 0.33 mol) was dissolved in DMA (700 mL) and cooled in ice bath under nitrogen. NaH (14.35 g, 60% in mineral oil, 0.363 mol) was added portionwise over a period of 20 min and the resulting mixture was continued to stir in ice bath for 10 min. Then iodomethane (21 mL, 0.363 mol) was added over a period of 10 min in ice bath and the mixture was stirred in ice bath for 10 min and then allowed to warm to room temperature and stirred for 1 h. The mixture was poured into ice water (2.5 L) and the resulting solid was filtered, washed with water, dried to give 98 g of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one.

Workup

  1. temperaturecooled in ice bath under nitrogen
  2. stirringthe mixture was stirred in ice bath for 10 min
  3. stirringstirred for 1 h
  4. filtrationthe resulting solid was filtered
  5. washwashed with water
  6. customdried

Sources & evidence

ORD record
ord-475b87f100e641f8ae20b336c547f428
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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