1. 1-Bromonaphthalene (10 g, 48.3 mmol) and acetyl chloride (4.2 ml, 58 mmol) were dissolved in 1,2-dichloroethane (100 ml) at 0 °C and aluminum chloride (14.4 g, 108 mmol) was added in batches.
2. The reaction mixture was stirred at room temperature for 24 hours.
3. The reaction mixture was poured into ice water (100 ml) and the organic and aqueous layers were separated.
4. The aqueous layer was extracted with ether (3 x 150 ml), the organic layers were combined and dried with magnesium sulfate.
5. After filtration, the solvent was removed under reduced pressure to give an orange colored oil.
6. Purification by fast chromatography (cyclohexane/ethyl acetate: 95/5) afforded 1-(4-bromo-1-naphthyl)ethanone as a yellow oil (91% yield).
7. 1-(4-bromo-1-naphthyl)ethanone was converted to its oxime derivative according to a method similar to that used for the preparation of compound 22 to afford a white powder (98% yield).
8. Activated zinc powder (24.7 g, 379 mmol) was added batchwise to a suspension of oxime (10.0 g, 37.9 mmol) in acetic acid (40 ml) and stirred at room temperature for 2 hours.
9. Zinc powder was removed by filtration and acetic acid was removed under reduced pressure.
10. Water (100 ml) was added and the pH was adjusted to 13 with 1N NaOH.
11. The aqueous layer was extracted with EtOAc (3 x 100 ml), the organic layers were combined and dried with MgSO4.
12. After filtration, the solvent was removed under reduced pressure to give a yellow oil (70% yield).
13. Boc2O (7.1 g, 31.8 mmol) was added to a 1,4-dioxane (50 ml) solution of amine (6.6 g, 26.5 mmol) and stirred at room temperature for 2 hours.
14. The solvent was removed under pressure and purified by fast chromatography (cyclohexane/EtOAc: 95/5) to give a yellow powder (75% yield).
15. Bromide (350 mg, 1 mmol) was dissolved in THF (13 ml)/water (2 ml), potassium acetate (100 mg, 1 mmol), 1,3-bis(diphenylphosphino)propane (9.0 mg, 0.02 mmol) and palladium(II) acetate (9.0 mg, 0.04 mmol) were added.
16. stirring for 3 hours at 50 atm CO pressure and 150 °C.
17. The reaction mixture was filtered, the filtrate was dried over MgSO4 and the solvent was removed under reduced pressure to give a yellow-green oil (300 mg).
18. Purification by fast chromatography (DCM/MeOH: 90/10) afforded 4-(1-tert-butoxycarbonylaminoethyl)-naphthalene-1-carboxylic acid as a white powder (14% yield).
19. The title product was prepared according to the procedure for compound 31 from 4-(1-tert-butoxycarbonylaminoethyl)-naphthalene-1-carboxylic acid (44 mg) and 4-aminopyridine (67% yield).
NMR data (300 MHz, DMSO-d6): δ 1.64 (d, 3H, J=6.6 Hz); 5.3 (q, 1H, J=6.5 Hz); 7.71 (m, 1H); 8.00 (d, 1H, J=7.7 Hz); 8.32 (m, 1H); 8.35 (d, 1H, J=7.3 Hz); 8.81 (d, 2H J=7.2Hz); 12.2 (s, 1H).
