Ammonia → 3-{1-[4-[3-chloro-4-[4-(3-dimethylaminopropyl)-1-piperazinyl]-phenyl]-1,4-dioxobutyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone

HRID 1766199Notes

Reaction equation

HRID 1766199 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:31])[CH2:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH2:16][CH2:15]2)=[O:13])[CH:5]=[CH:6][C:7]=1Cl.[CH3:32][N:33]([CH3:43])[CH2:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+].N>O.ClCCl.CO.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:31])[CH2:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:30])[CH2:16][CH2:15]2)=[O:13])[CH:5]=[CH:6][C:7]=1[N:40]1[CH2:41][CH2:42][N:37]([CH2:36][CH2:35][CH2:34][N:33]([CH3:32])[CH3:43])[CH2:38][CH2:39]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 27362341-[3-(Dimethylamino)propyl]piperazineHCID 211099083-{1-[4-(3,4-dichlorophenyl)-1,4-dioxobutyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone

Product 1

HCID 211098103-{1-[4-[3-chloro-4-[4-(3-dimethylaminopropyl)-1-piperazinyl]-phenyl]-1,4-dioxobutyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 921 mg (2.00 mmol) of 3-{1-[4-(3,4-dichloro-phenyl)-1,4-dioxobutyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone, 377 mg (2.2 mmol) of 1-(3-dimethylaminopropyl)-piperazine, 10 ml of DMSO and 0.276 g (2.00 mmol) of potassium carbonate was stirred for 24 hours at a reaction temperature of 85° C. The mixture was diluted with 200 ml of water, then extracted exhaustively with EE. The combined extracts were dried over sodium sulphate and concentrated by evaporation in vacuo. The residue remaining was purified twice by column chromatography on silica gel (Amicon, 35–70 μm) (dichloromethane/methanol/conc. ammonia 70/30/1 v/v/v as eluant). The appropriate eluates were combined and after working up in the usual way yielded 30.0 mg (2.5% of theoretical) of the desired substance as a colourless, amorphous substance. Rf 0.68 (El D) or 0.35 (eluant: dichloromethane/methanol/conc. ammonia 50/50/1 v/v/v). MS: M+594/596 (Cl); ESI: (M+H)+=595/597 (Cl)

Workup

  1. extractionextracted exhaustively with EE
  2. dry with materialThe combined extracts were dried over sodium sulphate
  3. concentrationconcentrated by evaporation in vacuo
  4. customThe residue remaining was purified twice by column chromatography on silica gel (Amicon, 35–70 μm) (dichloromethane/methanol/conc. ammonia 70/30/1 v/v/v as eluant)
  5. customyielded 30.0 mg (2.5% of theoretical) of the desired substance as a colourless, amorphous substance

Sources & evidence

ORD record
ord-a5bb4929918c427498412a954ccbc330
Source dataset
uspto-grants-2007_06
Patent number
US07230001B1

Reaction notes

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