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

HRID 1433059Notes

Reaction equation

HRID 1433059 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=C[C:21](C#N)=[C:20](N=C(C3C=CC=CC=3)C3C=CC=CC=3)[CH:19]=2)[C:13](=[O:40])[C@@H:12]1[CH2:41][CH2:42][S:43][CH3:44])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:45]1[CH:50]=[N:49][CH:48]=[N:47][CH:46]=1.C(O)(=O)C>C(O)C>[NH2:45][C:50]1[C:21]2[C:46](=[CH:23][C:18]([CH2:17][N:14]3[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[C@@H:12]([CH2:41][CH2:42][S:43][CH3:44])[C:13]3=[O:40])=[CH:19][CH:20]=2)[N:47]=[CH:48][N:49]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 92621,3,5-TriazineHCID 865925564-benzyloxycarbonyl-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one

Product 1

HCID 690288501-(4-Amino-quinazolin-7-ylmethyl)-4-benzyloxycarbonyl-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-oneYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-benzyloxycarbonyl-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-3-(S)-(2-methylsulfanyl-ethyl)-piperazin-2-one (1.17 g, 2.67 mmol) in 15 ml of ethanol is added 1,3,5-triazine and glacial acetic acid (3.1 ml, 53.4 mmol). The resulting solution is refluxed for 20 hours, concentrated under vacuum. The residue is dissolved in ethyle acetate, washed with 1N hydrochloric acid, a saturated aqueous NaHCO3 solution, water, brine. The solution is dried over MgSO4, concentrated. The resulting crude product is purified by column chromatography eluting with a gradient of 5% MeOH:CH2Cl2 to 10% MeOH:CH2Cl2. The title compound (489 mg, 39% yield) is obtained as a yellow solid.

Workup

  1. temperatureThe resulting solution is refluxed for 20 hours
  2. concentrationconcentrated under vacuum
  3. dissolutionThe residue is dissolved in ethyle acetate
  4. washwashed with 1N hydrochloric acid
  5. dry with materialThe solution is dried over MgSO4
  6. concentrationconcentrated
  7. customThe resulting crude product is purified by column chromatography
  8. washeluting with a gradient of 5% MeOH

Sources & evidence

ORD record
ord-b8ccc437339340e3a5eaec7a819b5e9a
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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