Sodium Carbonate → 8-(4-Chloro-5-methoxy-2-methylanilino)-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5]quinoline-7-carbonitrile

HRID 989315Notes

Reaction equation

HRID 989315 reaction equation
Cl[C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]([CH2:15][CH2:16][N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:8]3=[CH:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:23]#[N:24].[Cl:25][C:26]1[C:32]([O:33][CH3:34])=[CH:31][C:29]([NH2:30])=[C:28]([CH3:35])[CH:27]=1.Cl.N1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCCO)C.O>[Cl:25][C:26]1[C:32]([O:33][CH3:34])=[CH:31][C:29]([NH:30][C:4]2[C:3]([C:23]#[N:24])=[CH:2][C:11]3[CH:6]=[CH:7][C:8]4[N:14]([CH2:15][CH2:16][N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)[CH:13]=[N:12][C:9]=4[C:10]=3[N:5]=2)=[C:28]([CH3:35])[CH:27]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 10176127Pyridinium chlorideHCID 123258794-Chloro-5-methoxy-2-methylanilineHCID 219564158-chloro-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5-g]quinoline-7-carbonitrile

Product 1

HCID 693734258-(4-Chloro-5-methoxy-2-methylanilino)-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5]quinoline-7-carbonitrileYield 69.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8076Glycol monoethyl etherSolvent

Conditions

Temperature
132.5 °C

Procedure

A mixture of 86.5 mg (0.25 mmol) of 8-chloro-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5-g]quinoline-7-carbonitrile, 67.2 mg (0.39 mmol) of 4-chloro-5-methoxy-2-methyl aniline and 28.9 mg (0.25 mmol) of pyridine hydrochloride in 3 mL of 2-ethoxyethanol is heated at 130-135° C. for 11 hours. After cooling, the mixture is diluted with water and neutralized with 2 equivalents of sodium carbonate, and then extracted with ethyl acetate. The separated organic layer is washed with brine and dried over sodium sulfate. Removal of the solvent yields a residue which is purified on preparative TLC (developing solvent: 1:9 methanol/methylene chloride), giving 83.3 mg (69.9%) of the product as a beige solid, mp 246-248° C.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe separated organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. customRemoval of the solvent
  6. customyields a residue which
  7. customis purified on preparative TLC (developing solvent: 1:9 methanol/methylene chloride)

Sources & evidence

ORD record
ord-42f6f26acd8e48b9b6157e69918d5c7f
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

Loading…