3-[(2-Chloro-5-nitro-pyrimidin-4-yl)-(4-methoxy-benzyl)-amino]-2,2-difluoro-propionic acid ethyl ester → 2-Chloro-7,7-difluoro-9-(4-methoxy-benzyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 1676826Notes

Reaction equation

HRID 1676826 reaction equation
C([O:3][C:4](=O)[C:5]([F:28])([F:27])[CH2:6][N:7]([C:17]1[C:22]([N+:23]([O-])=O)=[CH:21][N:20]=[C:19]([Cl:26])[N:18]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)C>C(O)(=O)C.[Fe]>[Cl:26][C:19]1[N:20]=[CH:21][C:22]2[NH:23][C:4](=[O:3])[C:5]([F:28])([F:27])[CH2:6][N:7]([CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[C:17]=2[N:18]=1

Participants

4

Reactant 1

HCID 866375213-[(2-Chloro-5-nitro-pyrimidin-4-yl)-(4-methoxy-benzyl)-amino]-2,2-difluoro-propionic acid ethyl ester

Product 1

HCID 866375222-Chloro-7,7-difluoro-9-(4-methoxy-benzyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 41.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 1.9 g (0.0044 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-(4-methoxy-benzyl)-amino]-2,2-difluoro-propionic acid ethyl ester (IV-291) in 40 mL of acetic acid was added 1.9 g (0.034 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 and recrystallized from ethyl acetate to give 0.65 g of 2-chloro-7,7-difluoro-9-(4-methoxy-benzyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-291) as a white solid.

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. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-50c189229e2046a98018695da13a3f59
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

Loading…