Pyridinium chloride → 4-(3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile

HRID 269761Notes

Reaction equation

HRID 269761 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:19]#[N:20].[Cl:21][C:22]1[CH:23]=[C:24]([NH2:35])[CH:25]=[CH:26][C:27]=1[S:28][C:29]1[N:30]([CH3:34])[CH:31]=[CH:32][N:33]=1.Cl.N1C=CC=CC=1>C(OCCO)C>[Cl:21][C:22]1[CH:23]=[C:24]([CH:25]=[CH:26][C:27]=1[S:28][C:29]1[N:30]([CH3:34])[CH:31]=[CH:32][N:33]=1)[NH:35][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:19]#[N:20]

Participants

5

Reactant 3

HCID 10176127Pyridinium chlorideHCID 112206374-Chloro-7-(3-chloropropoxy)-6-methoxyquinoline-3-carbonitrileHCID 114590883-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamine

Product 1

HCID 684623414-(3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A 2.0 g (6.43 mmol) portion of 4-chloro-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile (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) in 2-ethoxyethanol (20 mL) is heated to 60° C. To this is added 1.7 g (7.10 mmol) of 3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)phenylamine (U.S. Pat. No. 4,973,599) and 0.74 g (6.43 mmol) of pyridine hydrochloride, and the resulting mixture is refluxed for 2 hours. After cooling, the precipitated solid is filtered, washed with aqueous sodium bicarbonate and dried in vacuo to give 2.93 g of 4-{3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]anilino}-7-(3-chloropropoxy)-6-methoxy-3-quinolinecarbonitrile as a tan solid, mp 271-276° C.

Workup

  1. temperatureAfter cooling
  2. filtrationthe precipitated solid is filtered
  3. washwashed with aqueous sodium bicarbonate
  4. customdried in vacuo

Sources & evidence

ORD record
ord-e8f40dd793ea421c99bf18f5bcc2ec35
Source dataset
uspto-grants-2008_11
Patent number
US07449460B2

Reaction notes

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