HCID 87619080, compound → HCID 87555250, compound

HRID 2111299Notes

Reaction equation

HRID 2111299 reaction equation
C([O:3][C:4](=O)[CH:5]([CH3:24])[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])[CH:5]([CH3:24])[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 87619080HCID 87619080, compound

Product 1

HCID 87555250HCID 87555250, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 2.27 g (0.0061 mole) of (rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclohexyl-amino]-2-methyl-propanoic acid ethyl ester in 40 mL of acetic acid was added 2.0 g (0.0358 g-atom) of iron powder. The mixture was heated at 80 degrees for 2 hours, and then filtered through Celite while still hot. The filtercake was washed with 100 mL of ethyl acetate and the combined filtrate was washed successively with 100 mL of water, 100 mL of 7.4 M ammonium hydroxide, 50 mL of water and then 100 mL of brine. The aqueous layers were back washed with 100 mL of ethyl acetate and the combined ethyl acetate layers dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with ethyl acetate-dichloromethane (1:1), followed by crystallization from dichloromethane-hexanes to give 1.48 g of (rac)-2-chloro-9-cyclohexyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-18) as white needles.

Workup

  1. temperatureThe mixture was heated at 80 degrees for 2 hours
  2. filtrationfiltered through Celite while still hot
  3. washThe filtercake was washed with 100 mL of ethyl acetate
  4. washthe combined filtrate was washed successively with 100 mL of water, 100 mL of 7.4 M ammonium hydroxide, 50 mL of water
  5. washThe aqueous layers were back washed with 100 mL of ethyl acetate
  6. dry with materialthe combined ethyl acetate layers dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with ethyl acetate-dichloromethane (1:1)
  11. customfollowed by crystallization from dichloromethane-hexanes

Sources & evidence

ORD record
ord-5d5ee23bbce845b6b9f5439cc1d48186
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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