Morpholine → 4-[(4-Chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile

HRID 2213805Notes

Reaction equation

HRID 2213805 reaction equation
[Cl:1][C:2]1[C:30]([O:31][CH3:32])=[CH:29][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]4[CH:20]=[C:19]([O:21][CH2:22][CH2:23]Cl)[C:18]([O:25][CH3:26])=[CH:17][C:14]=4[CH:15]=3)[N:10]=[CH:9][C:8]=2[C:27]#[N:28])=[C:4]([CH3:33])[CH:3]=1.[Cl:34][C:35]1[C:63]([O:64][CH3:65])=[CH:62][C:38]([NH:39][C:40]2[C:49]3[C:44](=[CH:45][C:46]4[CH:53]=[C:52]([O:54][CH3:55])[C:51]([O:56][CH2:57][CH2:58]Cl)=[CH:50][C:47]=4[CH:48]=3)[N:43]=[CH:42][C:41]=2[C:60]#[N:61])=[C:37]([CH3:66])[CH:36]=1.C([O-])(=O)C.[Na+].[NH:72]1[CH2:77][CH2:76][O:75][CH2:74][CH2:73]1>>[Cl:1][C:2]1[C:30]([O:31][CH3:32])=[CH:29][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]4[CH:20]=[C:19]([O:21][CH2:22][CH2:23][N:72]5[CH2:77][CH2:76][O:75][CH2:74][CH2:73]5)[C:18]([O:25][CH3:26])=[CH:17][C:14]=4[CH:15]=3)[N:10]=[CH:9][C:8]=2[C:27]#[N:28])=[C:4]([CH3:33])[CH:3]=1.[Cl:34][C:35]1[C:63]([O:64][CH3:65])=[CH:62][C:38]([NH:39][C:40]2[C:49]3[C:44](=[CH:45][C:46]4[CH:53]=[C:52]([O:54][CH3:55])[C:51]([O:56][CH2:57][CH2:58][N:72]5[CH2:77][CH2:76][O:75][CH2:74][CH2:73]5)=[CH:50][C:47]=4[CH:48]=3)[N:43]=[CH:42][C:41]=2[C:60]#[N:61])=[C:37]([CH3:66])[CH:36]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 517045Sodium AcetateHCID 115113674-(4-Chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrileHCID 116702254-(4-Chloro-5-methoxy-2-methylanilino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile

Product 2

HCID 53304264-(4-Chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrileHCID 53304354-[(4-Chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrileYield 23%

Conditions

Temperature
130 °C

Procedure

A mixture of 318 mg (0.66 mmol) of 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile and 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile (1:1 mixture), 100 mg of sodium acetate and 5 mL of morpholine is stirred and heated to 130° C. using an oil bath. After 30 minutes the reaction is allowed to cool to room temperature. The reaction mixture is concentrated in vacuo and the residue purified by silica gel chromatography, eluting with 95:5 methylene chloride/methanol to yield 82 mg (23%) of 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile as a yellow wax and 153 mg of 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 191–194° C. dec.

Workup

  1. temperatureto cool to room temperature
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. customthe residue purified by silica gel chromatography
  4. washeluting with 95:5 methylene chloride/methanol

Sources & evidence

ORD record
ord-59c991ff5ead4206a69730ba02af0b29
Source dataset
uspto-grants-2006_09
Patent number
US07105531B2

Reaction notes

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