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

HRID 2111334Notes

Reaction equation

HRID 2111334 reaction equation
C([O:5][C:6](=O)[CH2:7][CH2:8][N:9]([C:14]1[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]([Cl:23])[N:15]=1)[CH2:10][CH2:11][O:12][CH3:13])(C)(C)C.Cl>C(O)C>[Cl:23][C:16]1[N:17]=[CH:18][C:19]2[NH:20][C:6](=[O:5])[CH2:7][CH2:8][N:9]([CH2:10][CH2:11][O:12][CH3:13])[C:14]=2[N:15]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866234113-[(2-Chloro-5-nitro-pyrimidin-4-yl)-(2-methoxy-ethyl)-amino]-propanoic acid tert-butyl ester

Product 1

HCID 866234122-Chloro-9-(2-methoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 35.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3.3 g (0.0092 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-(2-methoxy-ethyl)-amino]-propanoic acid tert-butyl ester (IV-40) in 30 mL of ethanol was added 5.2 g (0.023 mole) of stannous chloride dihydrate and 1 mL of hydrochloric acid. The mixture was heated to 60 degrees for 2 hours and then concentrated under reduced pressure. The residue was taken up in 50 mL of water and extracted with three times with 50 mL of ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification of the residue by silica gel chromatography, eluting with dichloromethane-methanol (100:0-95:5) gave 0.84 g of 2-chloro-9-(2-methoxy-ethyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-40) as a white solid.

Workup

  1. temperatureThe mixture was heated to 60 degrees for 2 hours
  2. concentrationconcentrated under reduced pressure
  3. extractionextracted with three times with 50 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 of the residue by silica gel chromatography
  8. washeluting with dichloromethane-methanol (100:0-95:5)

Sources & evidence

ORD record
ord-d0a28d72f6254a9a90bbf98aaeb45616
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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