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

HRID 989361

Reaction equation

HRID 989361 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[CH:61]=[C:60]([Cl:62])[C:59]([O:63][CH3:64])=[CH:58][C:56]=1[NH2:57].C(OCCO)C>>[Cl:54][C:55]1[CH:61]=[C:60]([Cl:62])[C:59]([O:63][CH3:64])=[CH:58][C:56]=1[NH:57][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]

Participants

6

Reactant 5

HCID 8076Glycol monoethyl etherHCID 14766362,4-Dichloro-5-methoxyanilineHCID 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-carbonitrile

Product 1

HCID 115696394-(2,4-Dichloro-5-methoxyanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrileYield 48%

Conditions

Temperature
135 °C

Procedure

A mixture of 1.10 g (3.17 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), 50 mg of pyridine hydrochloride, 742 mg (3.86 mmol) of 2,4-dichloro-5-methoxyaniline and 25 mL of 2-ethoxyethanol is stirred and heated to 135° C. After 1 hour, the reaction is cooled to room temperature, quenched with 1.0 mL of triethylamine and concentrated in vacuo. The residue is dissolved in 95:5 methylene chloride/methanol and chromatographed on silica gel, eluting with 1:1 hexane/ethyl acetate. The product is precipitated from ethyl acetate to provide 0.760 g (48%) of 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile and 4-(2,4-dichloro-5-methoxyanilino)-8-methoxy-7(chloroethoxy)benzo[g]quinoline-3-carbonitrile (1:1 mixture) as a dull yellow solid, m.p. 239-55° C. dec.

Workup

  1. temperaturethe reaction is cooled to room temperature
  2. customquenched with 1.0 mL of triethylamine
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue is dissolved in 95:5 methylene chloride/methanol
  5. customchromatographed on silica gel
  6. washeluting with 1:1 hexane/ethyl acetate
  7. customThe product is precipitated from ethyl acetate

Sources & evidence

ORD record
ord-74b21ec7a4f74e91a6bed0248c332ccb
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Linked notes

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