1-bromononane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Polished shaved magnesium (3.2 g, 134 mmol) was heated, and thereafter, an anhydrous THF solution (68 ml) of 1-bromononane (12.9 ml, 67.5 mmol) was slowly added dropwise thereto. After heating to reflux for 1.5 hours, the reaction solution was cooled to a room temperature, and it was then added dropwise to a THF (80 mL) solution of the N-methoxy-N-methyldecanamide (4.8 g, 22.5 mmol) obtained by the method described in Production Example D-1-1. After the obtained mixture had been stirred for 30 minutes, 1 N hydrochloric acid was added to the reaction solution, followed by extraction with diethyl ether two times. Anhydrous magnesium sulfate was added to the organic layer to dry it, and the resultant was filtrated and was then concentrated. The obtained residue was purified using column chromatography (hexane:dichloromethane=8:1), so as to obtain 10-nonadecanone (6.0 g, 95%) as a ketone body in the form of a white amorphous solid. was heated After heating to reflux for 1.5 hours obtained by the method followed by extraction with diethyl ether two times Anhydrous magnesium sulfate was added to the organic layer to dry it the resultant was filtrated was then concentrated The obtained residue was purified

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

Procedure: 2,6-Diamino-9-(β-D-ribofuranosyl)purine (50 g, 180 mmol) was treated with sodium hydride (8.8 g, 220 mmol) and bromononane (59 g, 54.4 ml, 285 mmol) in DMF (700 ml) as per the procedure of Example 2 (the diamino compound in DMF was cooled in an ice bath during the addition of NaH) to yield 83 g of crude product. 50 g of crude product was purified by silica gel chromatography. Fraction containing 2'-O-nonyl and 3'-O-nonyl product were combined to give a 77:23 mixture (29 g) of the 2' and 3' product. Pure 2'-O-nonyl product is obtained by chromatography. 1H NMR (DMSO-d6) δ 0.95 (t, 3, CH3); 1.17 [m, 12, O--CH2 --CH2 --(CH2)6 ]; 1.42 [m, 2, O--CH2CH2 (CH2)6 ]; 3.27-3.70 (m, 2, H-5'); 3.50-3.70 [m, 2, O--CH2 (CH2)7 ]; 3.95 (m, 1, H-4'), 4.24 (m, 1, H-3'); 4.40 (m, 1, H-2'); 5.10 (d, 1, 3'-OH, J=5 Hz); 5.50 (t, 1, 5'-OH, J=6 Hz); 5.76 (s, 2, 2-NH2); 5.83 (d, 1, H-1', J=6.0 Hz); 6.81 (s, 2, 6-NH2); and 7.96 (s, 1, 8-H). to yield 83 g of crude product 50 g of crude product was purified by silica gel chromatography Fraction containing 2'-O-nonyl and 3'-O-nonyl product

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

Procedure: Following the procedure of Example 7 except substituting 1-bromopentane for 1-bromononane, ethoxylamine hydrochloride for methoxylamine hydrochloride and ethyl-3 iodovalerate for ethyl-4-iodobutyrate, and eliminating the addition of dicyclohexylamine, the title compound is obtained.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A magnetically stirred suspension of 1-bromononane (Aldrich, 40 g, 0.1931M) and triphenylphosphine (101.3 g, 0.3862 mole) was heated at 100° C. (oil bath) for 2 hours. The resulting homogeneous solution was then cooled and triturated with ether (8X) to remove most of the unreacted triphenylphosphine. A viscous gum was obtained which was dissolved in CH2Cl2 and concentrated in vacuo to give the title phosphonium salt as a light yellow, extremely hygroscopic foam weighing 85 g (80.1%). TLC, neat CH2Cl2, Rf =0.78, PMA. The resulting homogeneous solution was then cooled triturated with ether (8X) to remove most of the unreacted triphenylphosphine A viscous gum was obtained which concentrated in vacuo

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

Procedure: To a solution of 10 g of adenosine in 400 ml of dimethyl formamide was added 2.25 g of 60% sodium hydride (oil). After one hour, 8.5 ml of 1-bromononane was added. The reaction was stirred for 16 hours. Ice was added and the solution evaporated in vacuo. Water and ethyl acetate were added. The organic phase was separated, dried, and evaporated in vacuo to give a white solid, which was recrystallized from ethanol to yield 4.8 g of the title compound, m.p. 143°-144° C. analysis for: C19H31N5O4. Calculated: C, 57.99; H, 7.94; N, 1779. Found: C, 58.13; H, 7.93; N, 17.83. Ice was added the solution evaporated in vacuo Water and ethyl acetate were added The organic phase was separated dried evaporated in vacuo to give a white solid, which was recrystallized from ethanol

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

Procedure: 0.35 g of the crude 2-(3-fluoro-4-hydroxyphenyl)-5-(4-n-hexylphenyl)pyrazine was dissolved in 3 ml of dimethyl sulfoxide and 3 ml of tetrahydrofuran. To the resulting solution, was added 0.12 g of potassium-tertbutoxide. The obtained mixture was stirred at room temperature for 30 minutes and then 0.22 g of n-nonyl bromide was added thereto. The mixture was stirred at room temperature for additional five hours. Then the reaction mixture was diluted with ethyl acetate, washed with dilute hydrochloric acid and with a 30% aqueous solution of sodium hydroxide and then repeatedly washed with water until the washing liquor showed a pH value of approximately 7. Then the ethyl acetate phase was dehydrated over sodium sulfate and the solvent was distilled off. Thus 0.48 g of a crude reaction product was obtained. The crude reaction product was purified by silica gel column chromatography and recrystallized from acetone. Thus 0.41 g of the title compound was obtained. Phase transition temperature: 93.0° C. (C→Sc); The mixture was stirred at room temperature for additional five hours washed with dilute hydrochloric acid and with a 30% aqueous solution of sodium hydroxide repeatedly washed with water until the washing liquor the solvent was distilled off Thus 0.48 g of a crude reaction product was obtained The crude reaction product was purified by silica gel column chromatography recrystallized from acetone