Triethylamine → N-[2-(4-diphenylmethylpiperazin-1-yl)ethyl]-7-methyl-10-(2,3-dimethylpentanoylamino)-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxamide

HRID 652746Notes

Reaction equation

HRID 652746 reaction equation
[CH3:1][CH:2]([CH:25]([CH3:28])[CH2:26][CH3:27])[C:3]([NH:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([CH3:24])=[CH:11][N:12]3[C:19](=[O:20])[C:18]([C:21](O)=[O:22])=[CH:17][N:16]=[C:13]32)=[CH:8][CH:7]=1)=[O:4].C(N(CC)CC)C.ClC(OCC)=O.[C:42]1([CH:48]([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[N:49]2[CH2:54][CH2:53][N:52]([CH2:55][CH2:56][NH2:57])[CH2:51][CH2:50]2)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>ClCCl>[C:58]1([CH:48]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:49]2[CH2:50][CH2:51][N:52]([CH2:55][CH2:56][NH:57][C:21]([C:18]3[C:19](=[O:20])[N:12]4[CH:11]=[C:10]([CH3:24])[C:9]5[C:14]([C:13]4=[N:16][CH:17]=3)=[CH:15][C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:1])[CH:25]([CH3:28])[CH2:26][CH3:27])=[CH:7][CH:8]=5)=[O:22])[CH2:53][CH2:54]2)[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 47424562-(4-Benzhydrylpiperazino)ethaneamineHCID 1360680610-(2,3-dimethylpentanoylamino)-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylic acid

Product 1

HCID 13606825N-[2-(4-diphenylmethylpiperazin-1-yl)ethyl]-7-methyl-10-(2,3-dimethylpentanoylamino)-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxamideYield 75.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture containing 10-(2,3-dimethylpentanoylamino)-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylic acid (455 mg), triethylamine (0.174 ml) and dry dichloromethane (70 ml) was added slowly ethyl chloroformate (0.12 ml) at 0° C. under an inert atmosphere. After being stirred for 2 hours, a solution of 2-(4-diphenylmethyl-1-piperazinyl)-ethylamine (359 mg) in dry dichloromethane (10 ml) was added dropwise to the reaction mixture at 5° C. After stirring was continued for 12 hours at room temperature, the mixture was concentrated under reduced pressure. The residue was subjected to a column chromatography on silica gel with chloroform-methanol. The eluate was concentrated in vacuo to give residue, which was recrystallized from chloroform-ether to give N-[2-(4-diphenylmethylpiperazin-1-yl)ethyl]-7-methyl-10-(2,3-dimethylpentanoylamino)-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxamide (0.59 g).

Workup

  1. stirringAfter stirring
  2. waitwas continued for 12 hours at room temperature
  3. concentrationthe mixture was concentrated under reduced pressure
  4. concentrationThe eluate was concentrated in vacuo
  5. customto give residue, which
  6. customwas recrystallized from chloroform-ether

Sources & evidence

ORD record
ord-74b9b173864f433badf05d2e55677a8d
Source dataset
uspto-grants-1987_06
Patent number
US04673676

Reaction notes

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