1-(4-Aminoquinazoline-7-ylmethyl)-3-propyl-piperazine-2-one → 1-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione

HRID 1433062Notes

Reaction equation

HRID 1433062 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][NH:16][CH:15]([CH2:19][CH2:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.C([O:27][C:28](=O)[CH2:29][C:30]([C:32]1[S:33][C:34]([Cl:37])=[CH:35][CH:36]=1)=[O:31])(C)(C)C>N1C=CC=CC=1>[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:28](=[O:27])[CH2:29][C:30]([C:32]4[S:33][C:34]([Cl:37])=[CH:35][CH:36]=4)=[O:31])[CH:15]([CH2:19][CH2:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 179852681-(4-Aminoquinazoline-7-ylmethyl)-3-propyl-piperazine-2-oneHCID 670147073-(5-Chloro-thiophen-2-yl)-3-oxo-propionic acid tert-butyl ester

Product 1

HCID 872365911-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

The titled compound is prepared by a modification of a procedure published by Witzeman and Nottingham. (J. Org. Chem. 1991, 56, 1713.). 1-(4-Aminoquinazoline-7-ylmethyl)-3-propyl-piperazine-2-one (0.299 g, 1 mmol) and 3-(5-chloro-thiophen-2-yl)-3-oxo-propionic acid tert-butyl ester (0.287 g, 1.1 mmol) are dissolved in 10 ml of pyridine. The flask containing the resulting solution is placed in an oil bath preheated to 125° C. The reaction is heated with stirring under a stream of nitrogen gas for one hour until most of the pyridine had evaporated. The remaining pyridine is evaporated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2 to provide the product (0.48 g, 0.98 mmol). The product could be recrystallized from CH2Cl2/hexane to yield a yellow solid. M.P. 120-5° C. (dec). MS (ion spray) m/z 486, (M+H).

Workup

  1. additionThe flask containing the resulting solution
  2. customis placed in an oil bath
  3. custompreheated to 125° C
  4. temperatureThe reaction is heated
  5. customhad evaporated
  6. customThe remaining pyridine is evaporated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2

Sources & evidence

ORD record
ord-ba74a0eb3c7544f4944aa073de3a318d
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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