Hexane → HCID 22646572, compound

HRID 393653Notes

Reaction equation

HRID 393653 reaction equation
[C:1]([C:3]1[CH:20]=[CH:19][C:6]([NH:7][CH:8]=[C:9]2[C:14](=O)OC(C)(C)OC2=O)=[CH:5][C:4]=1[O:21][CH2:22][CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)#[N:2].CCCCCC.S(Cl)(Cl)=O.[F:41][C:42]1[CH:48]=[C:47]([CH3:49])[C:46]([OH:50])=[CH:45][C:43]=1[NH2:44]>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.C(O)(C)C.CN(C=O)C>[C:1]([C:3]1[CH:20]=[C:19]2[C:6](=[CH:5][C:4]=1[O:21][CH2:22][CH2:23][CH2:24][N:25]1[CH2:26][CH2:27][O:28][CH2:29][CH2:30]1)[N:7]=[CH:8][CH:9]=[C:14]2[NH:44][C:43]1[CH:45]=[C:46]([OH:50])[C:47]([CH3:49])=[CH:48][C:42]=1[F:41])#[N:2]

Participants

8

Reactant 4

HCID 8058HexaneHCID 24386Thionyl ChlorideHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 226465135-((4-Cyano-3-(3-morpholinopropoxy)anilino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 22646572HCID 22646572, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6228DimethylformamideSolventHCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)Solvent

Conditions

Temperature
250 °C

Procedure

A mixture of 5-((4-cyano-3-(3-morpholinopropoxy)anilino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione(2.96 g, 7 mmol) in DOWTHERM A, (trade mark of Fluka Chemie AG), (100 ml) was heated at 250° C. for 30 minutes. The mixture was allowed to cool, hexane was added and the solvent was decanted from the resulting gum. The residue was triturated with hexane to give crude 6-cyano-7-(3-morpholinopropoxy)-1,4-dihydroquinolin-4-one(1.0 g) as a brown solid. A portion of this product (380 mg, 1.3 mmol) was added to thionyl chloride (10 ml)and DMF (0.1 ml) and the mixture was heated at reflux for 3 hours. The volatiles were removed by evaporation and the residue was azeotroped with toluene (×3). 2-Fluoro-5-hydroxy-4-methylaniline (184 mg, 1.3 mmol), (prepared as described for the starting material in Example 1), in isopropanol (10 ml) was added to the residue, and the mixture was heated at reflux for 3 hours. The mixture was allowed to cool, the solid product was collected by filtration and recrystallised twice from methylene chloride/methanol/ethyl acetate to give 6-cyano-4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholinopropoxy)quinoline (05 mg, 3% overall).

Workup

  1. temperatureto cool
  2. customthe solvent was decanted from the resulting gum
  3. customThe residue was triturated with hexane
  4. customto give crude 6-cyano-7-(3-morpholinopropoxy)-1,4-dihydroquinolin-4-one(1.0 g) as a brown solid
  5. temperaturethe mixture was heated
  6. temperatureat reflux for 3 hours
  7. customThe volatiles were removed by evaporation
  8. customthe residue was azeotroped with toluene (×3)
  9. additionwas added to the residue
  10. temperaturethe mixture was heated
  11. temperatureat reflux for 3 hours
  12. temperatureto cool
  13. filtrationthe solid product was collected by filtration
  14. customrecrystallised twice from methylene chloride/methanol/ethyl acetate

Sources & evidence

ORD record
ord-49307f1447be429c99cdd5a24aaf803c
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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