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Process for preparing imidazopyridine derivatives

Assignee: Lonza AG
•
Filing: 1994-09-19
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Granted: 1995-08-29
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Expires: 2014-09-19
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Abstract

Abstract A process for preparing imidazopyridines of the general formula: ##STR1## wherein R 1 is an alkyl, cycloalkyl, aryl or aralkyl group or is a heterocyclic radical, R 2 and R 4 are identical or different and are hydrogen, a hydroxy, a cyano, alkyl, cycloalkyl, aryl or aralkyl group or are an alkanoyl or an alkoxy-carbonyl group, and R 3 is hydrogen, an alkyl, aryl or aralkyl group or a halogen atom. In the key step of the process, an amidine of the formula: ##STR2## is cyclized with a 1,3-dicarbonyl compound of the general formula: ##STR3## The imidazopyridines are valuable intermediates for the preparation of angiotensin II antagonists.

Inventors

  • 👤 Gerhard Stucky
  • 👤 Rene Imwinkelried

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-26 14:20
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04

Claims Analysis

Total Claims: 14
Claim 1
Independent Claim 217 words
Process for preparing an imidazopyridine derivative of formula: ##STR12## wherein R 1 is an alkyl, cycloalkyl, aryl or aralkyl group or is a heterocyclic radical, R 2 and R 4 are identical or different and are hydrogen, a hydroxy, a cyano, alkyl, cycloalkyl, aryl or aralkyl group or are an alkanoyl or an alkoxy-carbonyl group, and R 3 is hydrogen, an alkyl, aryl or aralkyl group or a halogen atom, comprising reacting a nitrile of formula: R.sub.1 CN II wherein R 1 is as defined above, with a thiol of formula: R.sub.5 SH III wherein R 5 is alkyl, aryl or aralkyl, in the presence of a hydrogen halide to give a thioimidate hydrohalide of formula: ##STR13## wherein R 1 and R 5 are as defined above and X is a halogen atom, reacting the thioimidate hydrohalide of formula IV with aminoacetonitrile to give an amidine of formula: ##STR14## wherein R 1 and X are as defined above, and finally cyclizing the amidine of formula V in the presence of a base with a 1,3-dicarbonyl compound of formula: ##STR15## wherein R 3 is as defined above and R 6 and R 7 are identical or different and are hydrogen or alkyl, cyano, cycloalkyl, alkanoyl, aryl, aralkyl, alkoxy or alkoxycarbonyl, to give the final product of formula I.
Claim 2
Dependent Claim 217 words
Process for preparing an imidazopyridine derivative of formula: ##STR12## wherein R 1 is an alkyl, cycloalkyl, aryl or aralkyl group or is a heterocyclic radical, R 2 and R 4 are identical or different and are hydrogen, a hydroxy, a cyano, alkyl, cycloalkyl, aryl or aralkyl group or are an alkanoyl or an alkoxy-carbonyl group, and R 3 is hydrogen, an alkyl, aryl or aralkyl group or a halogen atom, comprising reacting a nitrile of formula: R.sub.1 CN II wherein R 1 is as defined above, with a thiol of formula: R.sub.5 SH III wherein R 5 is alkyl, aryl or aralkyl, in the presence of a hydrogen halide to give a thioimidate hydrohalide of formula: ##STR13## wherein R 1 and R 5 are as defined above and X is a halogen atom, reacting the thioimidate hydrohalide of formula IV with aminoacetonitrile to give an amidine of formula: ##STR14## wherein R 1 and X are as defined above, and finally cyclizing the amidine of formula V in the presence of a base with a 1,3-dicarbonyl compound of formula: ##STR15## wherein R 3 is as defined above and R 6 and R 7 are identical or different and are hydrogen or alkyl, cyano, cycloalkyl, alkanoyl, aryl, aralkyl, alkoxy or alkoxycarbonyl, to give the final product of formula I.
Claim 3
Dependent Claim 16 words
The process according to claim 1 wherein the thioimidate hydrohalide of formula IV is not isolated.
Claim 4
Dependent Claim 46 words
The process according to claim 1 wherein the reaction to give the thioimidate hydrohalide of formua IV is carried out in the presence of hydrogen chloride and at a reaction temperature between 0° C. and room temperature, with or without the addition of an inert solvent.
Claim 5
Dependent Claim 33 words
The process according to claim 3 wherein the reaction to give the amidine of formula V is carried out at a temperature between 0° C. and the reflux temperature of the respective solvent.
Claim 6
Dependent Claim 21 words
The process according to claim 4 wherein the base used for the cyclization is an inorganic base or an organic base.
Claim 7
Dependent Claim 28 words
The process according to claim 5 wherein the base used for the cyclization is an alkali metal alkoxide, or an alkali metal hydroxide in a lower aliphatic alcohol.
Claim 8
Dependent Claim 30 words
The process according to claim 6 wherein the cyclization is carried out at a temperature between 0° C. and reflux temperature, in the presence or absence of an inert solvent.
Claim 9
Dependent Claim 21 words
The process according to claim 7 wherein the aminoacetonitrile is liberated from a salt of aminoacetonitrile by means of a base.
Claim 10
Dependent Claim 33 words
The process according to claim 1 wherein the reaction to give the amidine of formula V is carried out at a temperature between 0° C. and the reflux temperature of the respective solvent.
Claim 11
Dependent Claim 21 words
The process according to claim 1 wherein the base used for the cyclization is an inorganic base or an organic base.
Claim 12
Dependent Claim 28 words
The process according to claim 10 wherein the base used for the cyclization is an alkali metal alkoxide, or an alkali metal hydroxide in a lower aliphatic alcohol.
Claim 13
Dependent Claim 30 words
The process according to claim 1 wherein the cyclization is carried out at a temperature between 0° C. and reflux temperature, in the presence or absence of an inert solvent.
Claim 14
Dependent Claim 21 words
The process according to claim 1 wherein the aminoacetonitrile is liberated from a salt of aminoacetonitrile by means of a base.

References Cited (Backward Citations)

US4097525A Cited
EP0130461A2 Cited
EP0385850A2 Cited
US5066654A Cited
US5240938A Cited
EP0510813A1 Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1998-08-28 1999-02-27 1999-08-29 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2002-08-28 2003-02-27 2003-08-29 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2006-08-28 2007-02-27 2007-08-29 $7700.00 Window Closed / Lapsed

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