Pyridine based compounds useful as intermediates for pharmaceutical or agricultural end-products

• US 20090137558A1
• Filed: 12/01/2005
• Published: 05/28/2009
• Est. Priority Date: 12/03/2004
• Status: Abandoned Application

• Current Assignee: Peakdale Molecular Ltd. (Spectris PLC)
• Original Assignee: Peakdale Molecular Ltd. (Spectris PLC)
• Inventors: Fisher, Raymond, Lund, Andrew
• Application Number:
  US11/792,181
• Publication Number:
  US 20090137558A1
• Time in Patent Office: Days
• US Class Current: 514/217.70
• CPC Class Codes: C07D 213/50 Ketonic radicals
• CPC Class Codes: C07D 213/70 Sulfur atoms
• CPC Class Codes: C07D 213/73 Unsubstituted amino or imino radicals
• CPC Class Codes: C07D 213/80 in position 3
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 215/20 Oxygen atoms
• CPC Class Codes: C07D 221/16 containing carbocyclic rings other than six-membered
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention relates to substituted pyridine compounds of Formula (I) and derivatives thereof, and to a process for preparing these substituted pyridines. The invention also relates to the use of the substituted pyridines as intermediates in the production of pharmaceutical, chemical and agro-chemical products.

Claims

1-22. -22. (canceled)

23. A compound, or derivative thereof, of formula I

wherein R is a fluorinated C1-6 alkyl, COR³, CO₂R³, (CH₂)nCO₂R³ or (CH₂)nOR³ group optionally substituted by one or more of hydrogen, C1-6 alkyl or C1-6 haloalkyl, and wherein

n is 0 to 6;

R¹ and R² together are a group of formula (II)

wherein A and B, which form a bicyclic fused ring system with the ring of formula I, are C;

one or two of W, X, Y or Z is N;

R⁶, R⁷, R⁸ or R⁹ are independently selected from hydrogen, halogen, ═

O, ═

S, B(OR¹²)₂, C1-12 alkyl, C1-12 haloalkyl, cyclohydrocarbyl, heterocyclyl, OR¹², SR¹², NR¹²₂, NO₂, CN, NR¹²COR¹², NRCONR¹²₂, NRCOR¹², NR¹²CO₂R¹², S(O)₂R¹², SONR¹²₂, S(O)R¹², SO₂NR¹²₂, NR¹²S(O)₂R¹², COR¹², CO₂R¹², (CH₂)nOR¹², (CH₂)nCO₂R¹² or CONR¹²₂ optionally substituted by one or more of halogen, C1-6 alkyl, CO₂R¹³, (CH₂)nOR¹³, (CH₂)nCO₂R¹³, NR¹³R¹³ or heterocyclyl optionally substituted by NH₂;

wherein each saturated carbon in R⁶, R⁷, R⁸ or R⁹ is further optionally and independently substituted by ═

O, ═

S, ═

NR¹⁴, NNR¹⁴₂ or —

NOR¹⁴;

or wherein any two of R⁶, R⁷, R⁸ or R⁹ form a partially saturated, unsaturated or fully saturated optionally substituted five or six membered ring containing zero to three heteroatoms;

wherein R¹² which may be the same or different is hydrogen, halogen, CN, OR¹⁵, CO₂R¹⁵, NR¹⁵R¹⁵, C1-6 alkyl or heterocyclyl;

wherein R¹³ which may be the same or different is hydrogen, halogen, CN, OR¹⁶, NR¹⁶R¹⁶, optionally substituted C1-12 alkyl;

R¹⁴, R¹⁵ and R¹⁶ are hydrogen or OH; and

wherein n is 1 to 6.

or a pharmaceutically acceptable salt, and other pharmaceutically acceptable derivatives thereof.

24. The compound as claimed in claim 23 wherein R is fluorinated methyl or ethyl or is CO₂R³ wherein R³ is hydrogen or C1-6 alkyl.

25. The compound as claimed in claim 24 wherein R is CF₃ or CH₂F.

26. The compound as claimed in claim 23, 24, or 25 wherein R⁶, R⁷, R⁸ or R⁹ is independently selected from ═

O, CN, halogen, COR¹², CO₂R¹², NR¹²R¹², B(OR¹²)₂, (CH₂)nCO₂R¹², C1-6 alkyl, heterocyclyl optionally substituted by one or more of NR¹³R¹³ or heterocyclyl;

wherein each saturated carbon in R⁶, R⁷, R⁸ or R⁹ is further optionally and independently substituted by ═

O, ═

S, ═

NR¹⁴ or ═

NOR¹⁴;

wherein R¹² is hydrogen, halogen, NR¹⁵R¹⁵, C1-6 alkyl, or heterocyclyl;

wherein R¹³, R¹⁴ and R¹⁵ are hydrogen and wherein n is 1 or 2.

27. The compound as claimed in claim 26 wherein the R⁶, R⁷, R⁸ or R⁹ is optionally substituted piperidine or piperazine.

28. A process for the manufacture of a compound of formula I

wherein R and R¹ are the same or different and R is a fluorinated C1-6 alkyl, COR³, CO₂R³, (CH₂)nCO₂R³ or (CH₂)nOR³ group optionally substituted by one or more of hydrogen, C1-6 alkyl or C1-6 haloalkyl;

R¹ is NR³R³ or hydrocarbyl optionally substituted by one or more of halogen, CO₂R⁴, OR⁴, (CH₂)nOR⁴, (CH₂)nCO₂R³, NR⁴R⁴ or optionally substituted C1-6 alkyl;

R² is halogen, C1-6 alkyl, NO₂, CN, S(O)₂R³, COR³, CO₂R³, (CH₂)nOR³, (CH₂)nCO₂R³ or CONR³₂ optionally substituted by one or more of halogen, OR⁴, CN, C1-6 alkyl, CO₂R⁴, (CH₂)nOR⁴, (CH₂)nCO₂R³ or NR⁴R⁴;

wherein each saturated carbon in R² is further optionally and independently substituted by ═

O, ═

S, ═

NR⁵, NNR⁵₂ or ═

NOR⁵;

or R¹ and R² together form a partially saturated, unsaturated or fully saturated five or six membered ring containing zero to three heteroatoms which is further optionally fused to another partially saturated, unsaturated or fully saturated five or six membered ring to form a ring system containing zero to three heteroatoms, and each substitutable carbon atom in the optionally fused ring(s) or ring system(s) is optionally and independently substituted by one or more of halogen, ═

O, ═

S, C1-12 alkyl, C1-12 haloalkyl, cyclohydrocarbyl, heterocyclyl, OR³, SR³, NR³₂, NO₂, CN, NR³COR³, NRCONR³₂, NRCOR³, NR³CO₂R³, S(O)₂R³, SONR³₂, S(O)R³, SO₂NR³₂, NR³S(O)₂R³, COR³, CO₂R³, (CH₂)nOR³, (CH₂)nCO₂R³ or CONR³₂optionally substituted by one or more of halogen, optionally substituted C1-6 alkyl, CO₂R⁴, (CH₂)nOR⁴, (CH₂)nCO₂R⁴ or NR⁴R⁴;

R³ which may be the same or different and is hydrogen, halogen (Cl, F, I or Br), CN, OR⁵, CO₂R⁵, (CH₂)nNR⁵R⁵, NR⁵R⁵, (CH₂)nOH, C1-6 alkyl, heterocyclyl or aryl;

R⁴ which may be the same or different is hydrogen, halogen, CN, OR⁵, (CH₂)nNR⁵R⁵, NR⁵R⁵, optionally substituted C1-12 alkyl, heterocyclyl or aryl;

R⁵ which may be the same or different is hydrogen, halogen, C1-6 alkyl or C1-6 haloalkyl;

wherein n is 0 to 6;

the process comprising reacting a compound of formula IV with a compound of formula V or VI optionally in the presence of an ammonia source

wherein R and R¹ are the same or different and R is a fluorinated C1-6 alkyl, COR³, CO₂R³, (CH₂)nCO₂R³ or (CH₂)nOR³ group optionally substituted by one or more of hydrogen, C1-6 alkyl or C1-6 haloalkyl;

R¹ is NR³R³ or hydrocarbyl optionally substituted by one or more of halogen (F, Cl, Br, I), CO₂R⁴, OR⁴, (CH₂)nOR⁴, (CH₂)nCO₂R³, NR⁴R⁴ or optionally substituted C1-6 alkyl;

R² is halogen, C1-6 alkyl, NO₂, CN, S(O)₂R³, COR³, CO₂R³, (CH₂)nOR³, (CH₂)nCO₂R³ or CONR³₂ optionally substituted by one or more of halogen (F, Cl, Br, I), OR⁴, CN, C1-6 alkyl, CO₂R⁴, (CH₂)nOR⁴, (CH₂)nCO₂R³ or NR⁴R⁴;

wherein each saturated carbon in R² is further optionally and independently substituted by ═

O, ═

S, ═

NR⁵, NNR⁵₂ or ═

NOR⁵;

wherein R¹ and R² together optionally form a partially saturated, unsaturated or fully saturated five or six membered ring containing zero to three heteroatoms which is further optionally fused to another partially saturated, unsaturated or fully saturated five or six membered ring to form a ring system containing zero to three heteroatoms, and each substitutable carbon atom in the optionally fused ring(s) or ring system(s) is optionally and independently substituted by one or more of halogen (Cl, I, F or Br), ═

O, ═

S, C1-12 alkyl (e.g C1-6 alkyl), C1-12 haloalkyl, cyclohydrocarbyl, heterocyclyl, OR³, SR³, NR³₂, NO₂, CN, NR³COR³, NRCONR³₂, NRCOR³, NR³CO₂R³, S(O)₂R³, SONR³₂, S(O)R³, SO₂NR³₂, NR³S(O)₂R³, COR³, CO₂R³, (CH₂)nOR³, (CH₂)nCO₂R³ or CONR³₂ optionally substituted by one or more of halogen (F, Cl, Br, I), optionally substituted C1-6 alkyl, CO₂R⁴, (CH₂)nOR⁴, (CH₂)nCO₂R⁴ or NR⁴R⁴;

R³ which may be the same or different and is hydrogen, halogen (Cl, F, I or Br), CN, OR⁵, CO₂R⁵, (CH₂)nNR⁵R⁵, NR⁵R⁵, (CH₂)nOH, C1-6 alkyl (e.g methyl or ethyl), heterocyclyl or aryl;

R⁴ which may be the same or different is hydrogen, halogen, CN, OR⁵, (CH₂)nNR⁵R⁵, NR⁵R⁵, optionally substituted C1-12 alkyl (e.g C1-6), heterocyclyl or aryl;

R⁵ which may be the same or different is hydrogen, halogen (Cl, F, I or Br), C1-6 alkyl or C1-6 haloalkyl;

wherein n is 0 to 6;

R¹⁷ is hydrocarbyl;

X is O, NR¹⁸ or NR¹⁸₂ in protonated form and Y is NR¹⁸₂, wherein R¹⁸ is hydrogen;

and wherein when X is O the reaction must be carried out in the presence of a source of ammonia.

29. The process as claimed in claim 28 wherein when X is NR¹⁸₂ in protonated form, R¹ is NR¹⁹R¹⁹ or OR¹⁹ wherein R¹⁹ is hydrogen or C1-12 alkyl.