Claims
- 1. A process for the preparation of an amide of the formula: wherein: A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4 and A5 is nitrogen or CR5, with the proviso that at least one of the ring members A1 to A5 is nitrogen and that two nitrogen atoms are not bonded directly to one another; R1 to R5, if present, independently of one another are hydrogen, C1-4-alkyl or aryl, but one of the substituents R1 to R5 is a group of the formula —OR, wherein R is an optionally substituted aromatic or heteroaromatic radical, said optional substituents being ones which will not undergo alkylation; R6 is hydrogen or C1-4-alkyl; and R7 is an optionally substituted aromatic or heteroaromatic radical, comprising reacting a halogen compound of the formula: wherein A1 to A5 are as defined above and X is chlorine, bromine, or iodine, directly with carbon monoxide and a primary or secondary amine of the formula: R6—NH—R7 III wherein R6 and R7 are as defined above, in the presence of a complex of palladium with a triphenylphosphine of the formula: wherein R8 to R10 independently of one another are C1-4-alkyl, or fluorine, and with a base other than a primary or secondary or tertiary amine.
- 2. The process according to claim 1, wherein A2 is nitrogen and part of a pyridine ring.
- 3. The process according to claim 2, wherein R1 is a group of the formula —OR, R being an optionally substituted aromatic or heteroaromatic radical.
- 4. The process according to claim 3, wherein R is an optionally substituted phenyl group.
- 5. The process according to claim 1, wherein A1 is nitrogen and part of a pyridine ring.
- 6. The process according to claim 5, wherein R2 is a group of the formula —OR, R being an optionally substituted aromatic or heteroaromatic radical.
- 7. The process according to claim 1, wherein A1 and A5 are nitrogen and part of a pyrimidine ring.
- 8. The process according to claim 7, wherein R2 is a group of the formula —OR, R being an optionally substituted aromatic or heteroaromatic radical.
- 9. The process according to claim 1, wherein A1 and A4 are nitrogen and part of a pyrazine ring.
- 10. The process according to claim 9, wherein R2 is a group of the formula —OR, R being an optionally substituted aromatic or heteroaromatic radical.
- 11. The process according to claim 1, wherein A1, A3 and A5 are nitrogen.
- 12. The process according to claim 11, wherein R2 is a group of the formula —OR, R being an optionally substituted aromatic or heteroaromatic radical.
- 13. The process according to claim 12, wherein R is an optionally substituted phenyl group.
- 14. The process according to claim 12, wherein R6 is hydrogen and R7 is an optionally substituted phenyl group.
- 15. The process according to claim 14, wherein X is chlorine.
- 16. The process according to claim 1, wherein R6 is hydrogen and R7 is an optionally substituted phenyl group.
- 17. The process according to claim 1, wherein X is chlorine.
- 18. The process according to claim 15, wherein R8 to R10 are identical and are C1-4-alkyl groups.
- 19. The process according to claim 15 wherein R8 to R10 are fluorine.
- 20. The process according to claim 1, wherein R8 to R10 are identical and are C1-4-alkyl groups.
- 21. The process according to claim 1, wherein R8 to R10 are fluorine.
- 22. A process for the preparation of an amide of the formula: wherein:A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4 and A5 is nitrogen or CR5, with the proviso that at least one of the ring members A1 to A5 is nitrogen and that two nitrogen atoms are not bonded directly to one another; R1 to R5, if present, independently of one another are hydrogen, C1-4-alkyl or aryl, but one of the substituents R1 to R5 is a group of the formula —OR, wherein R is an optionally substituted aromatic or heteroaromatic radical; R6 is hydrogen or C1-4-alkyl; and R7 is an optionally substituted aromatic or heteroaromatic radical, said optional substituents being ones which will not undergo alkylation, comprising, in a first step, reacting a dihalide of the general formula: wherein A1 to A5 are as defined above, X is chlorine, bromine, or iodine, one of the radicals R1 to R5 on a carbon atom adjacent to a ring nitrogen atom is Z, Z being chlorine, bromine, or iodine, and the remaining radicals R1 to R5, if present, are as defined above, with an aromatic or heteroaromatic hydroxyl compound of the formula:R—OH VI wherein R is as defined above, to give a (hetero)aryloxy halogen compound of the formula: wherein A1 to A5 are as defined above, and, in a second step, reacting said product of formula II with carbon monoxide and a primary or secondary amine of the formula:R6—NH—R7 III wherein R6 and R7 are as defined above, in the presence of a complex of palladium with a triphenylphosphine of the formula: wherein R8 to R10 independently of one another are C1-4-alkyl, or fluorine, and with a base other than a primary or secondary or tertiary amine.
- 23. A process for the preparation of an amide of the formula wherein:A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4 and A5 is nitrogen or CR5, with the proviso that at least one of the ring members A1 to A5 is nitrogen and that two nitrogen atoms are not bonded directly to one another; R1 to R5, if present, independently of one another are hydrogen, C1-4-alkyl or aryl, but one of the substituents R1 to R5 is a group of the formula —OR, wherein R is an optionally substituted aromatic or heteroaromatic radical; R6 is hydrogen or C1-4-alkyl; and R7 is an optionally substituted aromatic or heteroaromatic radical, said optional substituents being ones which will not undergo alkylation, comprising reacting a halogen compound of the formula: wherein A1 to A5 are as defined above and X is chlorine, bromine, or iodine, directly with carbon monoxide and a primary or secondary amine of the formula:R6—NH—R7 III wherein R6 and R7 are as defined above, in the presence of a complex of palladium with a triphenylphosphine of the formula: wherein R8 to R10 independently of one another are C1-4-alkyl, C1-4-alkoxy, fluoro, or benzyloxy, provided at least one of R8, R9, and R10 is benzyloxy, and with a base other than k primary or secondary or tertiary amine.
- 24. The process of claim 23 wherein R8 to R10 are each benzyloxy.
- 25. A process for the preparation of an amide of the formula: wherein:A1 is nitrogen or CR1, A2 is nitrogen or CR2, A3 is nitrogen or CR3, A4 is nitrogen or CR4 and A5 is nitrogen or CR5, with the proviso that at least one of the ring members A1 to A5 is nitrogen and that two nitrogen atoms are not bonded directly to one another; R1 to R5, if present, independently of one another are hydrogen, C1-4-alkyl or aryl, but one of the substituents R1 to R5 is a group of the formula —OR, wherein R is an optionally substituted aromatic or heteroaromatic radical; R6 is hydrogen or C1-4-alkyl; and R7 is an optionally substituted aromatic or heteroaromatic radical, said optional substituents being ones which will not undergo alkylation, comprising, in a first step, reacting a dihalide of the general formula: wherein A1 to A5 are as defined above, X is chlorine, bromine, or iodine, one of the radicals R1 to R5 on a carbon atom adjacent to a ring nitrogen atom is Z, Z being chlorine, bromine, or iodine, and the remaining radicals R1 to R5, if present, are as defined above, with an aromatic or heteroaromatic hydroxyl compound of the formula:R—OH VI where R is as defined above, to give a (hetero)aryloxy halogen compound of the formula: wherein A1 to A5, R and X are as defined above, and, in a second step reacting said product of formula II with carbon monoxide and a primary or secondary amine of the formula:R6—NH—R7 III wherein R6 and R7 are as defined above, in the presence of a complex of palladium with a triphenylphosphine of the formula: wherein R8 to R10 independently of one another are C1-4-alkyl, C1-4-alkoxy, fluoro, or benzyloxy, provided at least one of R8, R9, and R10 is benzyloxy, and with a base other than said primary or secondary or tertiary amine. —
- 26. The process of claim 25 wherein R8 to R10 are each benzyloxy.
- 27. The process of claim 1 wherein the base is a carbonate, an acetate, a phosphate, or a hydrogen phosphate.
Priority Claims (2)
Number |
Date |
Country |
Kind |
1178/96 |
May 1996 |
CH |
|
2279/96 |
Sep 1996 |
CH |
|
Parent Case Info
This application is a division of 08/926,455, Sep. 10, 1997 now U.S. Pat. No. 5,900,484 which is a continuation-in-part of U.S. Ser. No. 08/850,393, filed on May 2, 1997 now U.S. Pat. No. 5,892,032.
US Referenced Citations (8)
Foreign Referenced Citations (4)
Number |
Date |
Country |
0053011 |
Jun 1982 |
EP |
0447004 |
Sep 1991 |
EP |
0582825 |
Feb 1994 |
EP |
WO 9427974 |
Dec 1994 |
WO |
Non-Patent Literature Citations (1)
Entry |
Ben-David et al., Journal of the American Chemical Society, vol. 111, No. 23, (1989), pp 8742-8744 J. Heterocycl. Chem., (1990), 27, 243. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08/850393 |
May 1997 |
US |
Child |
08/926455 |
|
US |