Benzyl Bromide → 9-Benzyl-2-chloro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2234402Notes

Reaction equation

HRID 2234402 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:14]=[C:13]2[C:7]([N:8]([CH3:16])[C:9](=[O:15])[CH2:10][CH2:11][NH:12]2)=[CH:6][N:5]=1.[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[NH4+]>CC(N(C)C)=O.CO>[CH2:17]([N:12]1[CH2:11][CH2:10][C:9](=[O:15])[N:8]([CH3:16])[C:7]2[C:13]1=[N:14][C:4]([Cl:3])=[N:5][CH:6]=2)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 866175762-Chloro-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 581538799-Benzyl-2-chloro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a cooled (ice/water bath) suspension of sodium hydride (60% dispersion in mineral oil; 6.5 mg, 0.16 mmol) in DMA (0.5 mL) was added a solution of 10-chloro-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 100; 32 mg, 0.15 mmol) in DMA (1.0 mL). The reaction mixture was allowed to stir, under nitrogen, in an ice bath for 15 minutes prior to addition of Benzyl bromide (Aldrich; 20 μl, 0.17 mmol). The reaction mixture was stirred on an ice bath for 15 minutes and then at ambient temperature for 3 hrs A further addition of Sodium hydride (2 mg) was made and stirring continued for 6 hrs. Saturated ammonium chloride (0.5 ml) was added and the reaction mixture poured directly onto an SCX-3 cartridge (2 g). The cartridge was washed with methanol (˜30 mL) before eluting products with 2M ammonia in methanol (˜30 mL). Product containing fractions were evaporated to dryness to give a colourless gum, which was combined with the cartridge methanol pre-wash and this solution evaporated to dryness. The resultant material was partitioned between DCM (10 mL) and water (10 mL). The organic phase was collected by gravity elution through a PTFE filter cup and evaporated to give the title compound as a pale yellow opaque gum (46 mg, 89%)

Workup

  1. temperatureTo a cooled
  2. stirringThe reaction mixture was stirred on an ice bath for 15 minutes
  3. stirringstirring
  4. waitcontinued for 6 hrs
  5. additionthe reaction mixture poured directly onto an SCX-3 cartridge (2 g)
  6. washThe cartridge was washed with methanol (˜30 mL)
  7. washbefore eluting products with 2M ammonia in methanol (˜30 mL)
  8. additionProduct containing fractions
  9. customwere evaporated to dryness
  10. customto give a colourless gum, which
  11. washpre-wash
  12. customthis solution evaporated to dryness
  13. customThe resultant material was partitioned between DCM (10 mL) and water (10 mL)
  14. customThe organic phase was collected by gravity elution through a PTFE
  15. filtrationfilter cup
  16. customevaporated

Sources & evidence

ORD record
ord-c858e5feea594a798628ddabf084cb50
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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