1-Chloro-4-(isocyanatomethyl)benzene → 4-(4-Aminoquinazolin-7-ylmethyl)-3-oxopiperazine-1-carboxylic acid 4-chloro-benzylamide

HRID 1432968Notes

Reaction equation

HRID 1432968 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][CH2:15][C:14]3=[O:19])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:20][C:21]1[CH:30]=[CH:29][C:24]([CH2:25][N:26]=[C:27]=[O:28])=[CH:23][CH:22]=1>CN(C=O)C>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:25][NH:26][C:27]([N:16]2[CH2:17][CH2:18][N:13]([CH2:12][C:8]3[CH:7]=[C:6]4[C:11]([C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)=[CH:10][CH:9]=3)[C:14](=[O:19])[CH2:15]2)=[O:28])=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 33723791-Chloro-4-(isocyanatomethyl)benzeneHCID 179851741-(4-Aminoquinazoline-7-ylmethyl)piperazine-2-one

Product 1

HCID 539247884-(4-Aminoquinazolin-7-ylmethyl)-3-oxopiperazine-1-carboxylic acid 4-chloro-benzylamideYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-aminoquinazoline-7-ylmethyl)piperazine-2-one (25 mg, 0.097 mmol), EXAMPLE 72, in 1 mL of DMF is added 4-chloro-benzyl isocyanate (22 mg, 0.13 mmol, prepared as described in EXAMPLE 37). After stirring 1 h at room temperature, the solution is concentrated. The crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are combined and lyopholized to provide the title compound (36 mg, 0.067 mmol) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ9.76 (bs, 2H), 8.83 (s, 1H), 8.38 (d, 1H), 7.64 (d, 1H), 7.60 (s, 1H), 7.34 (d, 2H), 7.31 (m, 1H), 7.26 (d, 2H), 4.75 (s, 2H), 4.22 (d, 2H), 4.08 (s, 2H), 3.60 (m, 2H), 3.35 (m, 2H). ESI MS, [M+H]+=425,427 (Cl pattern).

Workup

  1. concentrationthe solution is concentrated
  2. customThe crude product is purified by RP-HPLC
  3. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record
ord-4d6f940e91f04beeab04f99c513b8500
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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