Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
  • C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems

Definitions

• the present invention relates to a new process for the preparation of cinnamoyl-13 ⁇ baccatin III or deacetyl-10 baccatin III of general formula:
• OCOCgH 5 in which Rj represents an acetyl or 2,2,2-trichloroethoxycarbonyl radical.
• OCOC 6 H 5 by operating in an aromatic hydrocarbon in the presence of a condensing agent such as a carbodiimide (dicyclohexylcarbodiimide) or a reactive carbonate (dipyridyl-2 carbonate) and an activating agent such as dimethylaminopyridine at a temperature between 6 and 90 ° C.
• a condensing agent such as a carbodiimide (dicyclohexylcarbodiimide) or a reactive carbonate (dipyridyl-2 carbonate)
• an activating agent such as dimethylaminopyridine
• the product of general formula (I) can be obtained by the action of a mixed anhydride of cinnamic acid with a substituted benzoic acid on the derivative of baccatin III or 10-deacetyl baccatin III in basic medium using a mole of mixed anhydride per mole of baccatin III derivative or of 10-deacetyl baccatin m.
• R represents 1 to 5 substituents, identical or different, chosen from halogen atoms (chlorine, bromine) and nitro, methyl or methoxy radicals, can be obtained by the action of cinnamic acid on the acid chloride of a benzoic acid of general formula:
• the mixed anhydride of general formula (III) is obtained by the action of the acid chloride of general formula (IV) on cinnamic acid in solution in a suitable organic solvent such as tetrahydrofuran in the presence of a organic base such as a tertiary amine such as triethylamine at a temperature between 0 and 30 ° C.
• a suitable organic solvent such as tetrahydrofuran
• a organic base such as a tertiary amine such as triethylamine
• the reaction of the mixed anhydride of general formula (III) with the derivative of baccatin III or of desacetyl-10 baccatin III is carried out by slowly adding a solution mixed anhydride in an organic solvent suitable for a solution of the derivative of baccatin m or deacetyl-10 baccatin III in the same solvent in the presence of a condensing agent such as pyrrolidinopyridine or dimethylaminopyridine. It is particularly advantageous to operate under an inert atmosphere such as an argon atmosphere.
• an aromatic hydrocarbon is preferably used, chosen from benzene, toluene or xylenes, or an ether such as tetrahydrofuran.
• R represents a butoxy or phenyl radical and R'j represents a hydrogen atom or an acetyl radical according to the methods described in European patent applications EP-A-0253 738 and EP-A-0253 739.
• the toluene phase is washed with N hydrochloric acid, with sodium hydrogen carbonate in 2.5% aqueous solution and is then dried over sodium sulfate. After filtration and concentration to dryness under reduced pressure, the residue obtained is purified by chromatography on silica (0.015-0.025 mm), eluting with a toluene-ether mixture (95-5 by volume). 2.5 g of cinnamoyl-13 ⁇ bis- [(2,2,2-trichloroethoxy) carbonyloxy] -7 ⁇ , 10 ⁇ deacetyl-10 baccatin III, the characteristics of which are identical to, are obtained with a yield of 61.9%. those described by F. GUERITTE-VOEGELEIN et al., Tetrahedron, Vol. 42, No. 16, 4451-4460 (1986).

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Epoxy Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (3)

Publications (1)

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Family Applications Before (1)

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• 1991
  • 1991-07-25 FR FR9109424A patent/FR2679558B1/fr not_active Expired - Fee Related
• 1992
  • 1992-07-23 CZ CS94148A patent/CZ14894A3/cs unknown
  • 1992-07-23 NZ NZ243690A patent/NZ243690A/xx unknown
  • 1992-07-23 SK SK80-94A patent/SK8094A3/sk unknown
  • 1992-07-23 HU HU9400200A patent/HUT66773A/hu unknown
  • 1992-07-23 WO PCT/FR1992/000725 patent/WO1993002066A1/fr not_active Application Discontinuation
  • 1992-07-23 CA CA002113444A patent/CA2113444A1/fr not_active Abandoned
  • 1992-07-23 AU AU24168/92A patent/AU2416892A/en not_active Abandoned
  • 1992-07-23 MX MX9204323A patent/MX9204323A/es unknown
  • 1992-07-23 ZA ZA925560A patent/ZA925560B/xx unknown
  • 1992-07-23 EP EP92402123A patent/EP0526311A1/fr active Pending
  • 1992-07-23 EP EP92917152A patent/EP0598793A1/fr not_active Ceased
  • 1992-07-23 JP JP5502653A patent/JPH06508851A/ja active Pending
  • 1992-07-24 IE IE243392A patent/IE922433A1/en not_active Application Discontinuation
  • 1992-07-24 YU YU72892A patent/YU72892A/sh unknown
• 1994
  • 1994-01-24 NO NO940247A patent/NO940247L/no unknown
  • 1994-01-24 FI FI940338A patent/FI940338A/fi unknown

Non-Patent Citations (1)

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