Glycol monoethyl ether → 4-(4-Chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile

HRID 989359

Reaction equation

HRID 989359 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]3[CH:15]=[C:14]([O:16][CH2:17][CH2:18][Cl:19])[C:13]([O:20][CH3:21])=[CH:12][C:9]=3[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:22]#[N:23].ClC1C2C(=CC3C=C(OC)C(OCCCl)=CC=3C=2)N=CC=1C#N.Cl.N1C=CC=CC=1.[Cl:54][C:55]1[C:61]([O:62][CH3:63])=[CH:60][C:58]([NH2:59])=[C:57]([CH3:64])[CH:56]=1.C(OCCO)C>>[Cl:54][C:55]1[C:61]([O:62][CH3:63])=[CH:60][C:58]([NH:59][C:2]2[C:11]3[C:6](=[CH:7][C:8]4[CH:15]=[C:14]([O:16][CH2:17][CH2:18][Cl:19])[C:13]([O:20][CH3:21])=[CH:12][C:9]=4[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:22]#[N:23])=[C:57]([CH3:64])[CH:56]=1

Participants

6

Reactant 5

HCID 8076Glycol monoethyl etherHCID 10176127Pyridinium chlorideHCID 115157734-Chloro-7-methoxy-8-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrileHCID 116171834-Chloro-8-methoxy-7-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrileHCID 123258794-Chloro-5-methoxy-2-methylaniline

Product 1

HCID 115113674-(4-Chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrileYield 81.9%

Conditions

Temperature
135 °C

Procedure

A mixture of 248 mg (0.714 mmol) of 4-chloro-7-methoxy-8-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile and 4-chloro-8-methoxy-7-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile (1:1 mixture), 10 mg of pyridine hydrochloride, 150 mg (0.874 mmol) of 4-chloro-5-methoxy-2-methylaniline and 5 mL of 2-ethoxyethanol is stirred and heated to 135° C. After 1 hour, the reaction is cooled to room temperature, quenched with 0.2 mL of triethylamine and concentrated in vacuo. The residue is dissolved in 1:1 hexane/ethyl acetate with a little dichloromethane and chromatographed on silica gel eluting with 1:1 hexane/ethyl acetate, then ethyl acetate to provide 0.282 g of 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile and 4-(4-chloro-5-methoxy-2-methylamino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile (1:1 mixture) as a dull yellow solid (81%), m.p. 132-68° C. dec.

Workup

  1. temperaturethe reaction is cooled to room temperature
  2. customquenched with 0.2 mL of triethylamine
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue is dissolved in 1:1 hexane/ethyl acetate with a little dichloromethane
  5. customchromatographed on silica gel eluting with 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-9f3a9ad47e5d4368958fd307353f9211
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Linked notes

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