Process for preparing pyrano—[2,3-C]pyridine derivatives

1. A process comprising the step of dehydrating a compound of Formula (I):

to form a compound of Formula (II):

wherein R 1 is —CH═CH—R 8 or —CH 2 —CH═CH—R 9 ;

R 2 is C 1 -C 4 -alkyl;

R 3 is H, C 1 -C 4 -alkyl, benzyl, or -phenyl-(R 10 ) x ;

each R 4 is independently H, or C 1 -C 4 -alkyl;

each R 5 and each R 6 are independently H, C 1 -C 4 -alkyl, —O—C 1 -C 4 -alkyl, or —S—C 1 -C 4 -alkyl;

R 7 is R 8 or —CH 2 —R 9 ;

R 8 is H, C 1 -C 4 -alkyl, or -phenyl-(R 10 ) x ;

R 9 is H, C 1 -C 3 -alkyl, or -phenyl-(R 10 ) x ;

each R 10 is independently halo, C 1 -C 6 -alkyl, —O—C 1 -C 4 -alkyl, or —S—C 1 -C 4 -alkyl; and

each x is independently 0, 1, or 2 wherein the process is carried out in the presence of an organic base and a dehydrating agent selected from Tf 2 O or P 2 O 5 .

2. The process of claim 1 wherein R 4 , R 5 , and R 6 are each independently H or methyl; and the organic base is pyridine, triethylamine, or diisopropylethylamine.

3. The process of claim 2 wherein each of R 4 , R 5 , and R 6 is H; the dehydrating reagent is Tf 2 O; and the organic base is used in an amount of at least 1 equivalent with respect to the compound of Formula (I) and less than the amount of the dehydrating reagent, in equivalents.

4. The process of claim 1 or which further comprises the steps of:

a) reducing the compound of Formula (II) with a suitable reducing reagent to form a compound of Formula (III):

and

b) oxidizing the compound of Formula (III) with a suitable oxidizing reagent to form a compound of Formula (IV):

5. The process of claim 1 which further comprises the step of reducing the compound of Formula (II) with a suitable reducing reagent to form a compound of Formula (IV):

6. The process of claim 1 comprising the step of dehydrating a compound of Formula (V):

with a suitable dehydrating reagent to form a compound of Formula (VI):

wherein R 2 is C 1 -C 4 -alkyl.

7. The process of claim 6 wherein the dehydrating reagent is Tf 2 O or P 2 O 5 .

8. The process of claim 6 wherein the dehydrating reagent is Tf 2 O; and R 2 is methyl or ethyl.

9. The process of claim 6 wherein the process is carried out in the presence of an organic base in an amount of at least 1 equivalent with respect to the compound of Formula (V) and less than the amount of the dehydrating reagent, in equivalents.

10. The process of claim 6 which further comprises the steps of:

a) reducing the compound of Formula (VI) with a suitable reducing reagent to form a compound of Formula (VII):

and

b) oxidizing the compound of Formula (VII) with a suitable oxidizing reagent to form a compound of Formula (VIII):

11. The process of claim 6 which further comprises the step of reducing the compound of Formula (VI) with a suitable reducing reagent to form a compound of Formula (VIII):

12. The process of claim 4 wherein the reducing reagent is diisobutylaluminium hydride, LiAlH 4 , LiBH 4 , or NaBH 4 .

13. The process of claim 10 wherein the reducing agent is diisobutylaluminium hydride, LiAlH 4 , LiBH 4 , or NaBH 4 .

14. The process of claim 12 wherein the reducing reagent is LiBH 4 .

15. The process of claim 13 wherein the reducing reagent is LiBH 4 .

16. The process of claim 4 wherein the oxidizing reagent is MnO 2 , Swern oxidation reagents, 2-iodoxybenzoic acid, pyridine sulphur trioxide, or Dess-Martin periodinane.

17. The process of claim 10 wherein the oxidizing reagent is MnO 2 , Swern oxidation reagents, 2-iodoxybenzoic acid, pyridine sulphur trioxide, or Dess-Martin periodinane.

18. The process of claim 16 wherein the oxidizing reagent is pyridine sulphur trioxide.

19. The process of claim 17 wherein the oxidizing reagent is pyridine sulphur trioxide.

20. The process of claim 5 wherein the reducing reagent is diisobutylaluminium hydride.

21. The process of claim 11 wherein the reducing reagent is diisobutylaluminium hydride.