Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoate → 2-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

HRID 1676563Notes

Reaction equation

HRID 1676563 reaction equation
C([O:3][C:4](=O)[C:5]([F:24])([F:23])[CH2:6][N:7]([C:13]1[C:18]([N+:19]([O-])=O)=[CH:17][N:16]=[C:15]([Cl:22])[N:14]=1)[CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)C>C(O)(=O)C.[Fe]>[Cl:22][C:15]1[N:16]=[CH:17][C:18]2[NH:19][C:4](=[O:3])[C:5]([F:24])([F:23])[CH2:6][N:7]([CH:8]3[CH2:12][CH2:11][CH2:10][CH2:9]3)[C:13]=2[N:14]=1

Participants

4

Reactant 1

HCID 57955636Ethyl 3-[(2-chloro-5-nitropyrimidin-4-YL)(cyclopentyl)amino]-2,2-difluoropropanoate

Product 1

HCID 579556112-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneYield 60.7%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 6.16 g (0.016 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-difluoro-propanoic acid ethyl ester (IV-20) in 120 mL of acetic acid was added 6.0 g (0.11 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. Recrystallization of the residue with ethyl acetate and hexane gave 2.94 g of 2-chloro-9-cyclopentyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-20).

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. customRecrystallization of the residue with ethyl acetate and hexane

Sources & evidence

ORD record
ord-5d87187907fe4bd4bee4b6836d05dc97
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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