Cetraxate hydrochloride, DV-1006, Neuer

trans-3-[4-[4-(Aminomethyl)cyclohexylcarbonyloxy]phenyl]propionic acid hydrochloride

C17-H23-N-O4.Cl-H

341.8326

Daiichi Pharmaceutical (Originator)

Antiulcer Drugs, GASTROINTESTINAL DRUGS

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J Med Chem

Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity

By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in AcOH.

Atsuji, O.; et al.

Atsuji, O.; et al.; Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity. J Med Chem 1972, 15, 3, 247-255

J Med Chem1972,15,(3):247-255

Drugs Fut

Cetraxate

By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in AcOH.

Roberts, P.J.; Casta馿r, J.

Roberts, P.J.; Casta馿r, J.; Cetraxate. Drugs Fut 1977, 2, 8, 504

Drugs Fut1977,2,(8):504

Synthesis It can be obtained in two different ways: 1) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in HOAc (1,2) (Scheme 07020201a). 2) By condensation of trans-4-cyanocyclohexanecarbonyl chloride (III) and the benzyl ester (II) by means of triethylamine in hot benzene followed by debenzylation using H2 over Pd/C in acetic acid giving the cyanoester (IV), which is then reduced with H2 over Raney-Ni in ethyl acetate - ethanol - water (1) (Scheme 07020202a). 3) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and ter-butyl-4-hydroxyphenylpropionate (V) and performing the hydrolysis with HCl - acetic acid at room temperature (3) (Scheme 07020203a). Description Crystals, m.p. 280 C ; HCl salt, m.p. 238-40 C (dec.); Methanesulfonate salt, m.p. 213-5 C. Manufacturer Daiichi Seiyaku Co. References 1. Atsuji, O. et al.; Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity; J Med Chem 1972, 15(3), 247-255 2. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48075547 3. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48078143

J Med Chem

Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity

By condensation of trans-4-cyanocyclohexanecarbonyl chloride (III) and the benzyl ester (II) by means of triethylamine in hot benzene followed by debenzylation using H2 over Pd/C in acetic acid giving the cyanoester (IV), which is then reduced with H2 over Raney-Ni in ethyl acetate - ethanol - water.

Atsuji, O.; et al.

Atsuji, O.; et al.; Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity. J Med Chem 1972, 15, 3, 247-255

J Med Chem1972,15,(3):247-255

Drugs Fut

Cetraxate

By condensation of trans-4-cyanocyclohexanecarbonyl chloride (III) and the benzyl ester (II) by means of triethylamine in hot benzene followed by debenzylation using H2 over Pd/C in acetic acid giving the cyanoester (IV), which is then reduced with H2 over Raney-Ni in ethyl acetate - ethanol - water.

Roberts, P.J.; Casta馿r, J.

Roberts, P.J.; Casta馿r, J.; Cetraxate. Drugs Fut 1977, 2, 8, 504

Drugs Fut1977,2,(8):504

Synthesis It can be obtained in two different ways: 1) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in HOAc (1,2) (Scheme 07020201a). 2) By condensation of trans-4-cyanocyclohexanecarbonyl chloride (III) and the benzyl ester (II) by means of triethylamine in hot benzene followed by debenzylation using H2 over Pd/C in acetic acid giving the cyanoester (IV), which is then reduced with H2 over Raney-Ni in ethyl acetate - ethanol - water (1) (Scheme 07020202a). 3) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and ter-butyl-4-hydroxyphenylpropionate (V) and performing the hydrolysis with HCl - acetic acid at room temperature (3) (Scheme 07020203a). Description Crystals, m.p. 280 C ; HCl salt, m.p. 238-40 C (dec.); Methanesulfonate salt, m.p. 213-5 C. Manufacturer Daiichi Seiyaku Co. References 1. Atsuji, O. et al.; Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity; J Med Chem 1972, 15(3), 247-255 2. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48075547 3. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48078143

Drugs Fut

Cetraxate

By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and ter-butyl-4-hydroxyphenylpropionate (V) and performing the hydrolysis with HCl - acetic acid at room temperature.

Roberts, P.J.; Casta馿r, J.

Roberts, P.J.; Casta馿r, J.; Cetraxate. Drugs Fut 1977, 2, 8, 504

Drugs Fut1977,2,(8):504

Synthesis It can be obtained in two different ways: 1) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in HOAc (1,2) (Scheme 07020201a). 2) By condensation of trans-4-cyanocyclohexanecarbonyl chloride (III) and the benzyl ester (II) by means of triethylamine in hot benzene followed by debenzylation using H2 over Pd/C in acetic acid giving the cyanoester (IV), which is then reduced with H2 over Raney-Ni in ethyl acetate - ethanol - water (1) (Scheme 07020202a). 3) By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and ter-butyl-4-hydroxyphenylpropionate (V) and performing the hydrolysis with HCl - acetic acid at room temperature (3) (Scheme 07020203a). Description Crystals, m.p. 280 C ; HCl salt, m.p. 238-40 C (dec.); Methanesulfonate salt, m.p. 213-5 C. Manufacturer Daiichi Seiyaku Co. References 1. Atsuji, O. et al.; Medicinal chemical studies on antiplasmin drugs. 4. Chemical modification of trans-4-aminomethylcyclohexacarboxylic acid and its effect on antiplasmin activity; J Med Chem 1972, 15(3), 247-255 2. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48075547 3. Kitahara, S. (Daiichi Seiyaku Co., Ltd.); JP 48078143

JP 48075547

By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and benzyl 4-hydroxyphenylpropionate (II) by means of Et3N and hot benzene followed by debenzylation using H2 over Pd/C in AcOH.

Kitahara, S.

Kitahara, S.; . JP 48075547

JP 48075547,,():

JP 48078143

By condensation of trans-4-toluenesulfonylaminomethylcyclohexane carbonyl chloride (I) and ter-butyl-4-hydroxyphenylpropionate (V) and performing the hydrolysis with HCl - acetic acid at room temperature.

Kitahara, S.

Kitahara, S.; . JP 48078143

JP 48078143,,():