2,4-Dichloro-5-methoxyaniline → 8-(2-Chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile

HRID 989394Notes

Reaction equation

HRID 989394 reaction equation
Cl[C:2]1[C:3]2[CH:4]=[C:5]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH2:21][CH2:22][Cl:23])=[CH:14][C:6]3=[N:7][C:8]=2[N:9]=[CH:10][C:11]=1[C:12]#[N:13].[Cl:24][C:25]1[CH:31]=[C:30]([Cl:32])[C:29]([O:33][CH3:34])=[CH:28][C:26]=1[NH2:27]>C(OCCO)C>[Cl:23][CH2:22][CH2:21][O:20][C:15]1[C:16]([O:18][CH3:19])=[CH:17][C:5]2[C:6]([CH:14]=1)=[N:7][C:8]1[N:9]=[CH:10][C:11]([C:12]#[N:13])=[C:2]([NH:27][C:26]3[CH:28]=[C:29]([O:33][CH3:34])[C:30]([Cl:32])=[CH:31][C:25]=3[Cl:24])[C:3]=1[CH:4]=2

Participants

4

Reactant 2

HCID 14766362,4-Dichloro-5-methoxyanilineHCID 219564934-Chloro-8-(2-chloroethoxy)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile

Product 1

HCID 101641738-(2-Chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrileYield 41.2%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of 4-chloro-8-(2-chloroethoxy)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile (500 mg, 1.43 mmol) and 2,4-dichloro-5-methoxyaniline (460 mg, 2.39 mmol) in 40 mL of 2-ethoxyethanol is heated at reflux for 20 minutes then cooled to room temperature. The solution is partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is partitioned between ethyl acetate and an aqueous solution of sodium hydroxide and sodium bicarbonate (pH 14). The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. Ethyl acetate and diethyl ether are added to the residue and the resultant orange solid is collected by filtration to provide 297 mg (41%) of 8-(2-chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile, mp 227-230° C. dec.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 20 minutes
  3. customThe solution is partitioned between ethyl acetate and saturated sodium bicarbonate
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is partitioned between ethyl acetate
  8. dry with materialThe organic layer is dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. additionEthyl acetate and diethyl ether are added to the residue
  12. filtrationthe resultant orange solid is collected by filtration

Sources & evidence

ORD record
ord-e89bf325323a4cd4adb6b223b54b73b0
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

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