HCID 57955585, compound → 2-Chloro-9-cyclohexyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 1676776Notes

Reaction equation

HRID 1676776 reaction equation
C([O:3][C:4](=O)[C:5]([F:25])([F:24])[CH2:6][N:7]([C:14]1[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]([Cl:23])[N:15]=1)[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)C>C(O)(=O)C.[Fe]>[Cl:23][C:16]1[N:17]=[CH:18][C:19]2[NH:20][C:4](=[O:3])[C:5]([F:25])([F:24])[CH2:6][N:7]([CH:8]3[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]3)[C:14]=2[N:15]=1

Participants

4

Reactant 1

HCID 57955585HCID 57955585, compound

Product 1

HCID 579556702-Chloro-9-cyclohexyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 72.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 18 g (0.046 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclohexyl-amino]-2,2-difluoro-propionic acid ethyl ester (IV-246) in 100 mL of acetic acid was added 15.5 g (0.191 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. The organic layer was washed with ammonium hydroxide and water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The solid residue was washed with 50 mL of hexanes-EtOAc (90:10) and then air dried to give 10.5 g of 2-chloro-9-cyclohexyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-246).

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. washThe organic layer was washed with ammonium hydroxide and water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washThe solid residue was washed with 50 mL of hexanes-EtOAc (90:10)
  9. customair dried

Sources & evidence

ORD record
ord-d0a9d88ff8394ca99eb3d4400fd8308a
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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