Hydrochloric Acid → 2-Chloro-9-cyclopentyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2111285Notes

Reaction equation

HRID 2111285 reaction equation
C([O:3][C:4](=O)[CH2:5][CH2:6][N:7]([C:13]1[C:18]([N+:19]([O-])=O)=[CH:17][N:16]=[C:15]([Cl:22])[N:14]=1)[CH:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)C.Cl>C(O)C>[Cl:22][C:15]1[N:16]=[CH:17][C:18]2[NH:19][C:4](=[O:3])[CH2:5][CH2:6][N:7]([CH:8]3[CH2:12][CH2:11][CH2:10][CH2:9]3)[C:13]=2[N:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866234053-[(2-Chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-propanoic acid ethyl ester

Product 1

HCID 579403592-Chloro-9-cyclopentyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 65.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 0.356 g (0.001 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-propanoic acid ethyl ester (IV-10) in 5 mL of ethanol was added 0.562 g (0.0025 mole) of stannous chloride dihydrate and 0.1 mL of hydrochloric acid. The mixture was heated to 60 degrees for 2 hrs. The solvent was evaporated under reduced pressure. The residue was taken up in 20 mL of water and extracted with three times with 20 mL of ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (100:0-95:5) gave 0.174 g of 2-chloro-9-cyclopentyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-10) as a white solid.

Workup

  1. temperatureThe mixture was heated to 60 degrees for 2 hrs
  2. customThe solvent was evaporated under reduced pressure
  3. extractionextracted with three times with 20 mL of ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography
  8. washeluting with dichloromethane-methanol (100:0-95:5)

Sources & evidence

ORD record
ord-e10be9febbf8422891de313bcc9ca19f
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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