6-bromohexanamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Example 12(a), but reacting 640 mg (1.55 mmol) of methyl 4-[7-(1-adamantyl)-6-hydroxy-2-naphthyl]benzoate with 450 mg (2.32 mmol) of 6-bromohexanamide, 520 mg (65%) of the expected compound were obtained, which compound had a melting point of 209°-10° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 mg (0.121 mmol) of 8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine (S13-1) was dissolved in DMF (2 mL). 47 mg (0.145 mmol) of Cs2CO3 and 117.4 mg (0.605 mmol) of 6-bromohexanamide (S13-2) were added and the mixture was stirred at rt for 2 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9. 1H NMR (500 MHz, CDCl3/MeOH-d4): δ 8.13 (s, 1H), 7.31 (s, 1H), 6.97 (s, 1H), 5.98 (s, 2H), 4.13 (t, J=7.6 Hz, 2H), 2.14 (t, J=7.6 Hz, 2H), 1.71-1.80 (m, 2H), 1.55-1.65 (m, 2H), 1.28-1.39 (m, 2H); HRMS (ESI) m/z [M+H]+ calcd. for C18H20IN6O3S, 527.0362. found 527.0364. Solvent was removed under reduced pressure the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 mg (0.121 mmol) of 8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine (S13-1) was dissolved in DMF (2 mL). 47 mg (0.145 mmol) of Cs2CO3 and 117.4 mg (0.605 mmol) of 6-bromohexanamide (S13-2) were added and the mixture was stirred at rt for 2 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9. 1H NMR (500 MHz, CDCl3/MeOH-d4): δ 8.13 (s, 1H), 7.31 (s, 1H), 6.97 (s, 1H), 5.98 (s, 2H), 4.13 (t, J=7.6 Hz, 2H), 2.14 (t, J=7.6 Hz, 2H), 1.71-1.80 (m, 2H), 1.55-1.65 (m, 2H), 1.28-1.39 (m, 2H); HRMS (ESI) m/z [M+H]+ calcd. for C18H20IN6O3S, 527.0362. found 527.0364. Solvent was removed under reduced pressure the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Example 12(a), but reacting 640 mg (1.55 mmol) of methyl 4-[7-(1-adamantyl)-6-hydroxy-2-naphthyl]benzoate with 450 mg (2.32 mmol) of 6-bromohexanamide, 520 mg (65%) of the expected compound were obtained, which compound had a melting point of 209°-10° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By substituting 4-bromobutyl acetamide and 9-(4-pyridinylmethyl)-9H-fluorene in Ex. 1, the product was obtained in 100% yield; mp 50°-52° C. 1, the product was obtained in 100% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid phase synthesis has been employed in the preparation of certain pyridinones. In Solid Phase Synthesis of 1,3,5-Trisubstituted Pyridin-2-ones, Tetrahedron Letters, 40(1999) 2227-2230 authors James A. Linn et al. report the solid phase synthesis of 1,3,5-trisubstituted pyridin-2-ones via selective NH-alkylation of 3-amino-5-carbomethoxy-1H-pyridin-2-one using a solid supported halo-acid. The synthesis proceeds by the coupling of 6-bromohexanoic acid to a Rink amine macrocrown to form a solid-supported 6-bromohexanamide. The solid-supported 6-bromohexanamide was used to alklylate 3-amino-5-carbomethoxy-1H-pyridin-2-one which was then reacted with diphenylacetic acid. Saponification of the resulting ester yielded a solid supported carboxylic acid. Treatment of the solid supported carboxylic acid with pentafluorophenol provided the pentafluorophenyl ester, which when treated with benzylamine was cleaved from the macrocrown to give the pyridinone. However, a solid phase synthesis procedure to produce ring fused 2-pyridinones has not yet been reported. Solid phase synthesis

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By substituting 4-bromobutyl acetamide and 9-(4-pyridinylmethyl)-9H-fluorene in Ex. 1, the product was obtained in 100% yield; mp 50°-52° C. 1, the product was obtained in 100% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Example 12(a), but reacting 640 mg (1.55 mmol) of methyl 4-[7-(1-adamantyl)-6-hydroxy-2-naphthyl]benzoate with 450 mg (2.32 mmol) of 6-bromohexanamide, 520 mg (65%) of the expected compound were obtained, which compound had a melting point of 209°-10° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 mg (0.121 mmol) of 8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine (S13-1) was dissolved in DMF (2 mL). 47 mg (0.145 mmol) of Cs2CO3 and 117.4 mg (0.605 mmol) of 6-bromohexanamide (S13-2) were added and the mixture was stirred at rt for 2 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9. 1H NMR (500 MHz, CDCl3/MeOH-d4): δ 8.13 (s, 1H), 7.31 (s, 1H), 6.97 (s, 1H), 5.98 (s, 2H), 4.13 (t, J=7.6 Hz, 2H), 2.14 (t, J=7.6 Hz, 2H), 1.71-1.80 (m, 2H), 1.55-1.65 (m, 2H), 1.28-1.39 (m, 2H); HRMS (ESI) m/z [M+H]+ calcd. for C18H20IN6O3S, 527.0362. found 527.0364. Solvent was removed under reduced pressure the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 10:1) to give 12.7 mg (20%) of DZ5-49-N9