(Rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2-methyl-propanoic acid methyl ester → HCID 87555122, compound

HRID 2111378Notes

Reaction equation

HRID 2111378 reaction equation
C[O:2][C:3](=O)[CH:4]([CH3:21])[CH2:5][N:6]([C:11]1[C:16]([N+:17]([O-])=O)=[CH:15][N:14]=[C:13]([Cl:20])[N:12]=1)[CH:7]1[CH2:10][CH2:9][CH2:8]1>[Fe].C(O)(=O)C>[Cl:20][C:13]1[N:14]=[CH:15][C:16]2[NH:17][C:3](=[O:2])[CH:4]([CH3:21])[CH2:5][N:6]([CH:7]3[CH2:10][CH2:9][CH2:8]3)[C:11]=2[N:12]=1

Participants

4

Reactant 1

HCID 87619097(Rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2-methyl-propanoic acid methyl ester

Product 1

HCID 87555122HCID 87555122, compoundYield 52.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 2.54 g (0.0077 mole) of (rac)-3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2-methyl-propanoic acid methyl ester (IV-52) and 40 mL of acetic acid was added 2.5 g (0.0448 g-atom) of iron powder. The mixture was heated at 80 degrees for 3 hours, then filtered through Celite while still hot. The filter cake was washed with 100 mL of ethyl acetate. The filtrate was washed successively with 100 mL of water, 100 mL of 7.4 M ammonium hydroxide, 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 recrystallized from dichloromethane—hexanes to give 1.07 g of (rac)-2-chloro-9-cyclobutyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-52) 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 hydroxide, 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 recrystallized from dichloromethane—hexanes

Sources & evidence

ORD record
ord-b5fa6c3fb73743038b956bc805d197dd
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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