Methyl iodide → 2-Chloro-9-cyclohexyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2234518Notes

Reaction equation

HRID 2234518 reaction equation
[Cl:1][C:2]1[N:12]=[C:11]2[C:5]([NH:6][C:7](=[O:19])[CH2:8][CH2:9][N:10]2[CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:4][N:3]=1.[CH3:20]I.[H-].[Na+]>CC(N(C)C)=O>[Cl:1][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:20])[C:7](=[O:19])[CH2:8][CH2:9][N:10]2[CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866175922-Chloro-9-cyclohexyl-5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 714750712-Chloro-9-cyclohexyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 81.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
5 °C

Procedure

10-chloro-2-cyclohexyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 267; 5.87 g, 20.91 mmol) was suspended in DMA (450 mL) under nitrogen. Methyl iodide (3.26 g, 23 mmol) was added and the suspension cooled to 5° C. on an ice-water bath. Sodium hydride (60% mineral oil dispersion; 920 mg, 23 mmol) was added in a single portion and the resulting mixture stirred on the ice-water bath for 30 minutes allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL) and the solvent evaporated. The residue was partitioned between DCM (200 mL) and water (300 mL) and the aqueous phase re-extracted with DCM (100 mL). The combined organic phases were dried (MgSO4) and the evaporated. The residue was taken up in DCM and purified on a silica column eluting with a gradient of 10-50% EtOAc/isohexane over 10 column volumes. Fractions containing product were combined and evaporated to yield the title compound as a cream solid (5.02 g, 81%)

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (10 mL)
  3. customthe solvent evaporated
  4. customThe residue was partitioned between DCM (200 mL) and water (300 mL)
  5. extractionthe aqueous phase re-extracted with DCM (100 mL)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. custompurified on a silica column
  8. washeluting with a gradient of 10-50% EtOAc/isohexane over 10 column volumes
  9. additionFractions containing product
  10. customevaporated

Sources & evidence

ORD record
ord-8b79c4951ee446be9186b7fbded0a761
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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