Cyclopropanecarboxylic acid → Cyclopropyl-[4-(4-nitro-isoquinolin-1-yl)-piperazin-1-yl]-methanone

HRID 729614Notes

Reaction equation

HRID 729614 reaction equation
[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1)([O-:3])=[O:2].[CH:20]1([C:23](O)=[O:24])[CH2:22][CH2:21]1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.ClCCl>[CH:20]1([C:23]([N:17]2[CH2:16][CH2:15][N:14]([C:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][N:6]=3)[CH2:19][CH2:18]2)=[O:24])[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 15655Cyclopropanecarboxylic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 578328074-Nitro-1-piperazin-1-yl-isoquinoline

Product 1

HCID 57832816Cyclopropyl-[4-(4-nitro-isoquinolin-1-yl)-piperazin-1-yl]-methanoneYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Treat a solution or slurry of 4-nitro-1-piperazin-1-yl-isoquinoline (Preparation 26, 517 mg, 2 mmol), cyclopropanecarboxylic acid (258 mg, 3 mmol) and catalytic DMAP (24 mg, 0.2 mmol) in dichloromethane (20 mL) with EDCI (575 mg, 3 mmol). Agitate the resulting mixture at ambient temperature overnight, then wash with saturated aqueous sodium bicarbonate solution. Dry the organic layer over sodium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography using a gradient of 0-2% 2M ammonia-methanol in dichloromethane and a gradient of 0-70% ethyl acetate in hexanes to give a yellow solid after two purifications. (513 mg, 79% yield, LCMS ES+ (m/z) 327 [M+H]).

Workup

  1. washwash with saturated aqueous sodium bicarbonate solution
  2. dry with materialDry the organic layer over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customa gradient of 0-70% ethyl acetate in hexanes to give a yellow solid after two purifications

Sources & evidence

ORD record
ord-fa1cd912677440fb9bb9a1bfb6c4050e
Source dataset
uspto-grants-2009_09
Patent number
US07582638B2

Reaction notes

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