Claims
- 1. A process for the preparation of a compound of the formula: or an acid addition or base salt thereof, whereinR is phenyl optionally substituted by 1 to 3 substituents each independently selected from halo and trifluoromethyl; R1 is C1-C6 alkyl; and “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from C1-C6 alkyl, C1-C4 alkoxy, halo, oxo, benzyl and benzyloxy, comprising (a) reacting a compound of the formula: wherein R is as previously defined for a compound of the formula (I), with a compound of the formula wherein R1 and “Het” are as previously defined for a compound of the formula (I) and X is chloro, bromo or iodo, said reaction (a) taking place in the presence of zinc; at least one of iodine or a Lewis acid; and an aprotic organic solvent: optionally further reacting the resulting compound of step (a) with an acid or base to form the corresponding acid addition or base salt thereof.
- 2. A process as claimed in claim 1 wherein lead is also present.
- 3. A process as claimed in claim 1 wherein iodine is used.
- 4. A process as claimed in claim 3 which is carried out by mixing a solution or solutions of the compounds of the formulae (II) and (III) and iodine in an aprotic organic solvent with a mixture of zinc, iodine, optionally lead, optionally a Lewis acid, and an aprotic organic solvent.
- 5. A process as claimed in claim 1 wherein the Lewis acid, when used, is zinc chloride, zinc bromide or zinc iodide.
- 6. A process as claimed in claim 1 wherein the aprotic organic solvent is tetrahydrofuran.
- 7. A process as claimed in claim 1 wherein an acid addition salt of the compound of the formula (I) is prepared.
- 8. A process as claimed in claim 7 wherein the acid addition salt is the hydrochloride, hydrobromide, hydroiodide, sulphate, nitrate, methanesulphonate, camphorsulphonate, R-(−)-10-camphorsuphonate, (+)-3-bromo-10-camphorsulphonate, (−)-3-bromo-8-camphorsulphonate, phosphate, para-toluenesulphonate or benzenesulphonate salt.
- 9. A process as claimed in claim 1 wherein R is phenyl substituted by 1 or 2 substituents each independently selected from fluoro and chloro.
- 10. A process as claimed in claim 9 wherein R is phenyl substituted by 1 or 2 fluoro substituents.
- 11. A process as claimed in claim 10 wherein R is 2,4-difluorophenyl.
- 12. A process as claimed in claim 1 wherein R1 is methyl.
- 13. A process as claimed in claim 1 wherein “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from halo, oxo and benzyl.
- 14. A process as claimed in claim 13 wherein “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from fluoro, chloro, oxo and benzyl.
- 15. A process as claimed in claim 14 wherein “Het” is pyrimidinyl substituted by 1 to 3 substituents each independently selected from fluoro and chloro.
- 16. A process as claimed in claim 14 wherein “Het” is pyrimidin-4-yl, 4-chloro-5-fluoropyrimidin-6-yl, 5-fluoropyrimidin-4-yl, 2-chloro-5-fluoropyrimidin-6-yl, 2,4-dichloro-5-fluoropyrimidin-6-yl, 4-chloropyrimidin-6-yl or 1-benzyl-5-fluoropyrimidin-6-on-4-yl.
- 17. A process as claimed in claim 16 wherein “Het” is 4-chloro-5-fluoropyrimidin-6-yl.
- 18. A process as claimed in claim 1 wherein X is bromo.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9516121 |
Aug 1995 |
GB |
|
Parent Case Info
This application is a 371 of PCT/EP96/03376 filed Jul. 26, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/EP96/03376 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/06160 |
2/20/1997 |
WO |
A |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5364938 |
Dickinson et al. |
Nov 1994 |
A |
5567817 |
Ray et al. |
Oct 1996 |
A |
Foreign Referenced Citations (2)
Number |
Date |
Country |
357241 |
Mar 1990 |
EP |
440372 |
Aug 1991 |
EP |
Non-Patent Literature Citations (3)
Entry |
Crom and Hammond, “Organic Chemistry” McGraw-Hill Book Co., NY (1964) 2nd ed. pp 565-567.* |
R. P. Dickinson et al., Bioorganic & Medicinal Chemistry Letters, vol. 6, No. 16, pp. 2031-2036 (1996). |
D. George et al., Antimicrobial Agents and Chemotherapy, pp. 86-91 (Jan. 1996). |