Triethylamine → HCID 22470537, compound

HRID 395016Notes

Reaction equation

HRID 395016 reaction equation
Cl.Cl.Cl[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][C:9]([CH2:17][CH2:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][C:21]=2[F:32])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]1.[SH:33][C:34]1[S:35][CH2:36][CH2:37][N:38]=1.C(N(CC)CC)C>CN(C)C=O.O>[F:32][C:21]1[CH:22]=[N:23][C:24]2[C:29]([C:20]=1[CH2:19][CH2:18][CH2:17][C:9]1([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:10][CH2:11][N:6]([CH2:5][CH2:4][S:33][C:34]3[S:35][CH2:36][CH2:37][N:38]=3)[CH2:7][CH2:8]1)=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 22469796HCID 22469796, compoundHCID 178527880HCID 178527880, compound

Product 1

HCID 22470537HCID 22470537, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.7 g of ethyl 1-(2-chloroethyl)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate dihydrochloride, 0.18 g of 2-mercaptothiazoline and 0.63 cm3 of triethylamine in 10 cm3 of dimethylformamide was stirred under an inert atmosphere for 23 hours at a temperature in the region of 80° C. After cooling to about 20° C., the reaction mixture was taken up in water, extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was added to a solution of 0.18 g of 2-mercaptothiazoline and 0.06 g of 10% sodium hydride in 10 cm3 of dimethylformamide, and the mixture was then heated at a temperature in the region of 80° C. for 15 hours. After cooling to about 20° C., the reaction mixture was taken up in water, extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under atmospheric pressure on a column of silica gel (particle size 70-200μ; diameter 2 cm; mass 40 g), eluting with a mixture of dichloromethane/ethanol (95/5 by volume) and collecting 10-cm3 fractions. Fractions 11 to 24 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.15 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(4,5-dihydrothiazol-2-ylthio)ethyl]piperidine-4-carboxylate was obtained in the form of a brown oil.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. extractionextracted with ethyl acetate
  3. washwashed with saturated sodium chloride solution
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  7. additionThe evaporation residue was added to a solution of 0.18 g of 2-mercaptothiazoline and 0.06 g of 10% sodium hydride in 10 cm3 of dimethylformamide
  8. temperaturethe mixture was then heated at a temperature in the region of 80° C. for 15 hours
  9. temperatureAfter cooling to about 20° C.
  10. extractionextracted with ethyl acetate
  11. washwashed with saturated sodium chloride solution
  12. dry with materialThe organic phase was dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  15. customThe residue obtained
  16. customwas purified by chromatography under atmospheric pressure on a column of silica gel (particle size 70-200μ; diameter 2 cm; mass 40 g)
  17. washeluting with a mixture of dichloromethane/ethanol (95/5 by volume)
  18. customcollecting 10-cm3 fractions
  19. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-09a257a3044b44ba97c898d0ec7f738d
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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