Morpholine → 4-(2,4-Dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrile

HRID 2213840Notes

Reaction equation

HRID 2213840 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[C:6]([O:32][CH3:33])=[CH:7][C:8]2[C:9]([CH:31]=1)=[N:10][C:11]1[N:12]=[CH:13][C:14]([C:29]#[N:30])=[C:15]([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:16]=1[CH:17]=2.[I].[Na].[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>>[Cl:28][C:20]1[CH:21]=[C:22]([Cl:27])[C:23]([O:25][CH3:26])=[CH:24][C:19]=1[NH:18][C:15]1[C:16]2[CH:17]=[C:8]3[CH:7]=[C:6]([O:32][CH3:33])[C:5]([O:4][CH2:3][CH2:2][N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:31][C:9]3=[N:10][C:11]=2[N:12]=[CH:13][C:14]=1[C:29]#[N:30]

Participants

4

Reactant 3

HCID 8083MorpholineHCID 101641738-(2-Chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrileHCID 178506594HCID 178506594, compound

Product 1

HCID 101662684-(2,4-Dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrileYield 47%

Procedure

A mixture of 8-(2-chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile (202 mg, 0.40 mmol) and sodium iodine (70 mg, 0.47 mmol) in 4 mL of morpholine is heated at reflux for 2 hours. The reaction mixture is concentrated in vacuo and partitioned between ethyl acetate and water. The organic layer is washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated in vacuo. Ethyl acetate is added to the residue and the orange solid is collected by filtration to provide 105 mg (47%) of 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrile, mp 242–244° C. dec. MS 553.8, 555.8 (M+H)+ Analysis for C27H25Cl2N5O4 Calcd: C, 58.49; H, 4.54; N, 12.63. Found: C, 58.41; H, 4.23; N, 12.48.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 2 hours
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer is washed with saturated sodium bicarbonate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionEthyl acetate is added to the residue
  10. filtrationthe orange solid is collected by filtration

Sources & evidence

ORD record
ord-66742b13fa874fe18cec29c8e7a28c54
Source dataset
uspto-grants-2006_09
Patent number
US07105531B2

Reaction notes

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