HCID 86637525, compound → 2-Chloro-9-cyclopentyl-7,7-dichloro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 1676837Notes

Reaction equation

HRID 1676837 reaction equation
C[O:2][C:3](=O)[C:4]([Cl:23])([Cl:22])[CH2:5][N:6]([C:12]1[C:17]([N+:18]([O-])=O)=[CH:16][N:15]=[C:14]([Cl:21])[N:13]=1)[CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1>C(O)(=O)C.[Fe]>[Cl:21][C:14]1[N:15]=[CH:16][C:17]2[NH:18][C:3](=[O:2])[C:4]([Cl:23])([Cl:22])[CH2:5][N:6]([CH:7]3[CH2:11][CH2:10][CH2:9][CH2:8]3)[C:12]=2[N:13]=1

Participants

4

Reactant 1

HCID 86637525HCID 86637525, compound

Product 1

HCID 866375262-Chloro-9-cyclopentyl-7,7-dichloro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 35.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 2.2 g (0.0056 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-dichloro-propanoic acid methyl ester (IV-298) in 40 mL of acetic acid was added 2.2 g (0.039 g-atom) of iron powder. The mixture was heated to 80 degrees for 2 hours and then filtered while hot. Water and ethyl acetate were added to the filtrate and the mixture was stirred for 10 minutes and then filtered. The layers were separated. The organic layer was washed successively with ammonium hydroxide and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with hexane-ethyl acetate (gradient, 95:5-50:50) gave 0.66 g of 2-chloro-9-cyclopentyl-7,7-dichloro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-298).

Workup

  1. temperatureThe mixture was heated to 80 degrees for 2 hours
  2. filtrationfiltered while hot
  3. additionWater and ethyl acetate were added to the filtrate
  4. filtrationfiltered
  5. customThe layers were separated
  6. washThe organic layer was washed successively with ammonium hydroxide and water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customPurification by silica gel chromatography
  15. washeluting with hexane-ethyl acetate (gradient, 95:5-50:50)

Sources & evidence

ORD record
ord-92acb80b86cf48978112171a2b93a63a
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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