Hydrochloric Acid → 6-Amino-4-(3-chloro-4-(pyrid-2-ylmethoxy)phenylamino)-7-ethoxyquinoline-3-carbonitrile

HRID 403657Notes

Reaction equation

HRID 403657 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH2:17][CH3:18])=[C:9]([NH:12]C(=O)C)[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:19]#[N:20].[Cl:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)[NH2:25].CS(O)(=O)=O.Cl.C(=O)([O-])[O-].[K+].[K+]>C(O)C.CO>[NH2:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:16][CH2:17][CH3:18])[N:5]=[CH:4][C:3]([C:19]#[N:20])=[C:2]2[NH:25][C:24]1[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)=[C:22]([Cl:21])[CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6395Methanesulfonic AcidHCID 11430Potassium CarbonateHCID 11358234N-(4-Chloro-3-cyano-7-ethoxy-6-quinolinyl)acetamideHCID 167812123-Chloro-4-(2-pyridylmethoxy)aniline

Product 1

HCID 252676486-Amino-4-(3-chloro-4-(pyrid-2-ylmethoxy)phenylamino)-7-ethoxyquinoline-3-carbonitrileYield 71.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide (11.64 g, 0.04 mol, 1.00 equiv), 3-chloro-4-(pyridin-2-ylmethoxy)aniline (9.53 g, 0.04 mol, 1.00 equiv), methanesulfonic acid (1.3 ml, 0.02 mol, 0.5 equiv) in ethanol (30 ml) was stirred under refluxed for 6 hours and then 0.6N hydrogen chloride (600 ml, 0.36 mol) was added. The mixture was heated to 80° C. for additional 19 hours, and then cooled to 0° C. where the precipitated solids were formed and filtered. The product was added to a solution of 1N potassium carbonate (200 ml, 0.2 mol) in methanol (300 ml) and the resulting mixture was stirred for 3 hours. The resulting precipitated solids were filtered, washed with 1:1 methanol/water (500 ml) and dried to give 12.8 g of product. MS (ESI) m/z: 446 (M+1).

Workup

  1. temperatureunder refluxed for 6 hours
  2. temperaturecooled to 0° C. where the precipitated solids
  3. customwere formed
  4. filtrationfiltered
  5. stirringthe resulting mixture was stirred for 3 hours
  6. customThe resulting precipitated solids
  7. filtrationwere filtered
  8. washwashed with 1:1 methanol/water (500 ml)
  9. customdried

Sources & evidence

ORD record
ord-9254c6d471304d62acda53bad991ef03
Source dataset
uspto-grants-2014_06
Patent number
US08748453B2

Reaction notes

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