(Rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-butanoic acid ethyl ester → (Rac)-2-chloro-9-cyclopentyl-8-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2111275Notes

Reaction equation

HRID 2111275 reaction equation
C([O:3][C:4](=O)[CH2:5][CH:6]([N:8]([C:14]1[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]([Cl:23])[N:15]=1)[CH:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1)[CH3:7])C>C(O)(=O)C.[Fe]>[Cl:23][C:16]1[N:17]=[CH:18][C:19]2[NH:20][C:4](=[O:3])[CH2:5][CH:6]([CH3:7])[N:8]([CH:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[C:14]=2[N:15]=1

Participants

4

Reactant 1

HCID 87555928(Rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-butanoic acid ethyl ester

Product 1

HCID 87617702(Rac)-2-chloro-9-cyclopentyl-8-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 5.3%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 1.07 g (0.030 mole) of (rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-butanoic acid ethyl ester in 20 mL of acetic acid was added 1.0 g (0.018 g-atom) of iron powder. The mixture was heated to 80 degrees for 2 hrs and then filtered while hot. 50 mL of water and 50 mL of ethyl acetate were added and the mixture was stirred for 10 minutes and then filtered. The layers were separated. The organic layer was washed with ammonium hydroxide and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (100:0-96:4) gave 0.45 g of (rac)-2-chloro-9-cyclopentyl-8-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-3) as a white solid.

Workup

  1. temperatureThe mixture was heated to 80 degrees for 2 hrs
  2. filtrationfiltered while hot
  3. addition50 mL of water and 50 mL of ethyl acetate were added
  4. filtrationfiltered
  5. customThe layers were separated
  6. washThe organic layer was washed with ammonium hydroxide and water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by silica gel chromatography
  11. washeluting with dichloromethane-methanol (100:0-96:4)

Sources & evidence

ORD record
ord-e81fc271a85b406c8ec12d73edc37c94
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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