Hydrochloric Acid → 2-Chloro-9-cyclohexyl-5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one

HRID 2111305Notes

Reaction equation

HRID 2111305 reaction equation
C([O:5][C:6](=O)[CH2:7][CH2:8][N:9]([C:16]1[C:21]([N+:22]([O-])=O)=[CH:20][N:19]=[C:18]([Cl:25])[N:17]=1)[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)(C)(C)C.C(O)C.Cl>C(OCC)(=O)C.O>[Cl:25][C:18]1[N:19]=[CH:20][C:21]2[NH:22][C:6](=[O:5])[CH2:7][CH2:8][N:9]([CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[C:16]=2[N:17]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 866234063-[(2-Chloro-5-nitro-pyrimidin-4-yl)-cyclohexyl-amino]-propionic acid tert-butyl ester

Product 1

HCID 866175922-Chloro-9-cyclohexyl-5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-oneYield 41.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.53 g (0.004 mole) of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclohexyl-amino]-propionic acid tert-butyl ester (IV-20) in 20 mL of ethyl acetate was added in portions over 10 minutes to a mixture of 2.69 g (0.012 mole) of stannous chloride dihydrate, 12 mL of ethanol and 0.5 mL of hydrochloric acid. The mixture was stirred overnight and then diluted with 30 mL of water and extracted with ethyl acetate. The ethyl acetate extract was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (100:0-92:8) to give 0.47 g of 2-chloro-9-cyclohexyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-20).

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe ethyl acetate extract
  3. dry with materialwas dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with dichloromethane-methanol (100:0-92:8)

Sources & evidence

ORD record
ord-278512b9d9664f3d8a820781f3b30f0c
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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