1-(4-Amino-quinazolin-7-ylmethyl)-4-benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one → 1-(4-Amino-quinazolin-7-ylmethyl)-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one

HRID 1433060Notes

Reaction equation

HRID 1433060 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16](C(OCC4C=CC=CC=4)=O)[C@@H:15]([CH2:29][CH2:30][S:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1>Br.C(O)(=O)C.CCOCC>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][NH:16][C@@H:15]([CH2:29][CH2:30][S:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 1

HCID 690288501-(4-Amino-quinazolin-7-ylmethyl)-4-benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one

Product 1

HCID 670141251-(4-Amino-quinazolin-7-ylmethyl)-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-oneYield 42%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolventHCID 3283Diethyl EtherSolvent

Procedure

1-(4-Amino-quinazolin-7-ylmethyl)-4-benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one (100 mg, 0.215 mmol) is dissolved in 5 ml of 30% hydrogen bromide in acetic acid. The mixture is stirred for 1 hour, diluted with ethyle ether. The ether is decanted and the resulting solid is washed thoroughly with ethyle ether. The resulting crude product is purified by column chromatography eluting with a 4/2/1 mixture of CH2Cl2/MeOH/NH4OH (30% in H2O). with a gradient of 5% MeOH:CH2Cl2 to 10% MeOH:CH2Cl2. The resulting product is purified by another column chromatography eluting with a gradient of 20% MeOH:CH2Cl2 to 50% MeOH:CH2Cl2. The title bound (30 mg, 42% yield) is obtained as an off-white solid.

Workup

  1. customThe ether is decanted
  2. washthe resulting solid is washed thoroughly with ethyle ether
  3. customThe resulting crude product is purified by column chromatography
  4. washeluting with a 4/2/1 mixture of CH2Cl2/MeOH/NH4OH (30% in H2O)
  5. customThe resulting product is purified by another column chromatography
  6. washeluting with a gradient of 20% MeOH
  7. customis obtained as an off-white solid

Sources & evidence

ORD record
ord-dd90b56c3fbe4e41b3c761cc6d155dbc
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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