1,4'-Bipiperidine → 7-(3-[1,4'-Bipiperidin]-1'-ylpropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile

HRID 269783Notes

Reaction equation

HRID 269783 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:18][C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([Cl:27])=[CH:21][C:20]=3[Cl:28])=[C:11]([C:16]#[N:17])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:29][CH3:30].[N:31]1([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>COCCOC>[N:31]1([CH:37]2[CH2:42][CH2:41][N:40]([CH2:2][CH2:3][CH2:4][O:5][C:6]3[CH:15]=[C:14]4[C:9]([C:10]([NH:18][C:19]5[CH:24]=[C:23]([O:25][CH3:26])[C:22]([Cl:27])=[CH:21][C:20]=5[Cl:28])=[C:11]([C:16]#[N:17])[CH:12]=[N:13]4)=[CH:8][C:7]=3[O:29][CH3:30])[CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

4

Reactant 2

HCID 786071,4'-BipiperidineHCID 110489207-(3-Chloropropoxy)-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinoline-3-carbonitrile

Product 1

HCID 252528627-(3-[1,4'-Bipiperidin]-1'-ylpropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrileYield 10.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 260 mg (0.56 mmol) of 7-(3-chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-6-methoxyquinoline-3-carbonitrile (Boschelli, Diane H.; Ye, Fei; Wang, Yanong D.; Dutia, Minu; Johnson, Steve L.; Wu, Biqi; Miller, Karen; Powell, Dennis W.; Yaczko, Deanna; Young, Mairead; Tischler, Mark; Arndt, Kim; Discafani, Carolyn; Etienne, Carlo; Gibbons, Jay; Grod, Janet; Lucas, Judy; Weber, Jennifer M.; Boschelli, Frank. J. Med. Chem. 2001, 44, 3965-3977) and 380 mg (2.24 mmol) of [1,4′]bipiperidinyl are heated in 3 mL of ethylene glycol dimethyl ether at 85° C. for sixteen hours to yield the crude product. Following removal of the solvent in vacuo, the crude product is purified by silica gel chromatography (eluting with 7:3 methylene chloride/methanol) to give 35 mg of 7-(3-[1,4′-bipiperidin]-1′-ylpropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile as a white solid, mp 130-132° C.

Workup

  1. customto yield the crude product
  2. customremoval of the solvent in vacuo
  3. customthe crude product is purified by silica gel chromatography (eluting with 7:3 methylene chloride/methanol)

Sources & evidence

ORD record
ord-5a18e1918b744d4a965f58a103e8bd90
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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