HCID 87556169, compound → HCID 87617683, compound

HRID 2111360Notes

Reaction equation

HRID 2111360 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][O: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][O:11][CH2:10][CH2:9]3)[C:14]=2[N:15]=1

Participants

4

Reactant 1

HCID 87556169HCID 87556169, compound

Product 1

HCID 87617683HCID 87617683, compoundYield 57.7%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 3.55 g of (rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-(tetrahydro-pyran-4-yl)-amino]-2-methyl-propanoic acid ethyl ester (IV-45) in 40 mL of acetic acid was added 3.5 g (0.0627 g-atom) of iron powder. The mixture was heated at 80 degrees for 3 hours, and then filtered through Celite while still hot. The filter cake was washed with 100 mL of ethyl acetate and the filtrate was washed successively with 100 mL of water, 100 mL of 7.4 M ammonium 100 mL of water and 100 mL of brine. The aqueous layers were back extracted with 100 mL of ethyl acetate. The ethyl acetate layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-ethyl acetate (40:60-0:100), followed by recrystallization from dichloromethane—hexanes to give 1.63 g of (rac)-2-chloro-7-methyl-9-(tetrahydro-pyran-4-yl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-45) as white crystalline solid.

Workup

  1. temperatureThe mixture was heated at 80 degrees for 3 hours
  2. filtrationfiltered through Celite while still hot
  3. washThe filter cake was washed with 100 mL of ethyl acetate
  4. washthe filtrate was washed successively with 100 mL of water, 100 mL of 7.4 M ammonium 100 mL of water and 100 mL of brine
  5. extractionThe aqueous layers were back extracted with 100 mL of ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with dichloromethane-ethyl acetate (40:60-0:100)
  11. customfollowed by recrystallization from dichloromethane—hexanes

Sources & evidence

ORD record
ord-7e11826fabe346eea00fb5b05008aa37
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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