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

HRID 2234415Notes

Reaction equation

HRID 2234415 reaction equation
[Cl:1][C:2]1[N:12]=[C:11]2[C:5]([NH:6][C:7](=[O:20])[C:8]([CH3:19])([CH3:18])[CH2:9][N:10]2[CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:4][N:3]=1.[CH3:21]I.[H-].[Na+]>CC(N(C)C)=O>[Cl:1][C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:21])[C:7](=[O:20])[C:8]([CH3:18])([CH3:19])[CH2:9][N:10]2[CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 581540122-Chloro-9-cyclopentyl-7,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×

Product 1

HCID 592951162-Chloro-9-cyclopentyl-5,7,7-trimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 92%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of 10-chloro-2-cyclopentyl-4,4-dimethyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-8,10,12-trien-5-one (Intermediate 127; 9.67 g, 32.8 mmol) in DMA (710 mL) under nitrogen was added methyl iodide (2.25 mL, 36.08 mmol). The mixture was cooled in ice/water to 2.5° C. Sodium hydride (60% dispersion in mineral oil, 1.45 g, 36.08 mmol) was added in one portion. A small exotherm to 4° C. was observed. The reaction mixture was stirred on an ice/water bath for 1 hour, and then stirred at room temperature overnight. Solvent was removed in vacuo and the light-brown liquid residue was treated with water. This afforded a solid, which was filtered off and washed with water. The solid material was dissolved in DCM (200 mL) and the solution dried using MgSO4, filtered and evaporated to give an off white solid which was purified on a 330 g Si column (Companion). loading as a solution in DCM (60 mL) The column having been equilibrated with 30% Ethyl Acetate in isohexane, and eluted with 30% Ethyl Acetate in isohexane for the first 5 minutes and then with a linear gradient slowly rising to 100% Ethyl Acetate. Product containing fractions were combined and evaporated to dryness to give the title compound as a white solid (9.29 g, 92%)

Workup

  1. customto 4° C.
  2. stirringstirred at room temperature overnight
  3. customSolvent was removed in vacuo
  4. additionthe light-brown liquid residue was treated with water
  5. customThis afforded a solid, which
  6. filtrationwas filtered off
  7. washwashed with water
  8. dissolutionThe solid material was dissolved in DCM (200 mL)
  9. customthe solution dried
  10. filtrationfiltered
  11. customevaporated
  12. customto give an off white solid which
  13. customwas purified on a 330 g Si column (Companion)
  14. washeluted with 30% Ethyl Acetate in isohexane for the first 5 minutes
  15. additionProduct containing fractions
  16. customevaporated to dryness

Sources & evidence

ORD record
ord-05f60f0cd0ca4b41aafe454c5fc114e2
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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