Glycol monoethyl ether → 4-(4-Hydroxy-2-methyl-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile

HRID 612212Notes

Reaction equation

HRID 612212 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:24]#[N:25].[NH2:26][C:27]1[C:28]([CH3:34])=[CH:29][C:30]([OH:33])=[CH:31][CH:32]=1.Cl.N1C=CC=CC=1.C(OCCO)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[OH:33][C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:24]#[N:25])=[C:28]([CH3:34])[CH:29]=1

Participants

7

Reactant 5

HCID 8076Glycol monoethyl etherHCID 178194-Amino-m-cresolHCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 224666014-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline-3-carbonitrile

Product 1

HCID 224666904-(4-Hydroxy-2-methyl-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrileYield 61.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.3 g of 4chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile derivative, 0.12 g of 4amino-m-cresol, 0.1 g of pyridine hydrochloride and 4 ml of 2-ethoxy ethanol was stirred under nitrogen at reflux temperature for 1.5 hr. The mixture was cooled and added to the mixture of ethyl acetate and saturated solution of sodium bicarbonate, stirred for 15 minutes. Following separation of layers, the organic layer was dried over anhydrous sodium sulfate, filtered and filtrate was evaporated to yield dark oil. The oil was purified by silica gel flash chromatography utilizing a gradient of methylene chloride/methanol (95:5 to 90:10 ) to give 0.23 g of the title compound as a tan solid, mp120-126 C; mass spectrum (electrospray, m/e):M+H 449.

Workup

  1. temperatureat reflux temperature for 1.5 hr
  2. temperatureThe mixture was cooled
  3. stirringstirred for 15 minutes
  4. customseparation of layers
  5. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customfiltrate was evaporated
  8. customto yield dark oil
  9. customThe oil was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-f1670b9cd6974024861328f172222743
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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