1-isocyanatohexadecane

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

Procedure: 1.34 ml (5 meq) of hexadecyl isocyanate and 0.7 ml (5 meq) of 3-dimethylaminopropylamine are combined in 5 ml of tetrahydrofuran and reacted over a weekend at room temperature. The reaction mixture is filtered, washed with tetrahydrofuran, dried in vacuo and recrystallized from acetone to yield 1.2 gm of title compound with a m.p. of 78°-79° C. reacted over a weekend at room temperature The reaction mixture is filtered washed with tetrahydrofuran dried in vacuo recrystallized from acetone

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

Procedure: 1.34 ml (5 meq) of hexadecyl isocyanate and 0.7 ml (5 meq) of 3-dimethylaminopropylamine are combined in 5 ml of tetrahydrofuran and reacted over a weekend at room temperature. The reaction mixture is filtered, washed with tetrahydrofuran, dried in vacuo and recrystallized from acetone to yield 1.2 gm of title compound with a m.p. of 78°-79° C. reacted over a weekend at room temperature The reaction mixture is filtered washed with tetrahydrofuran dried in vacuo recrystallized from acetone

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

Procedure: The title compound is prepared by the procedure of Example 11, using 50.0 mg (52 μmol) of 16-({[5-(aminomethyl)-4-hydroxy-3-methoxytetrahydro-2-furanyl]oxy}{5-[2,4-dioxo-3,4-dihydro-1 (2H)-pyrimidinyl]-3,4-dihydroxytetrahydro-2-furanyl}methyl)-9-(1-hydroxy-2-methylpropyl)-6-(2-iminohexahydro-4-pyrimidinyl)-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioic acid (λmax nm in water=259) and 14.0 mg (52 μmol) hexadecyl isocyanate in 2.0 ml of N,N-dimethyl formamide to give 3.0 mg of the desired product. The title compound is prepared by the procedure of Example 11

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

Procedure: (5.1) To a stirring solution of 5-amino-3-methyl-thiophene-2,4-dicarboxylic acid 2-octyl ester 4-tert-butyl ester (348 mg, 0.94 mmol) and DBU (0.35 mL, 360 mg, 2.4 mmol) in CH2Cl2 (10 mL) was added octyl isocyanate (0.166 mL, 146 mg, 0.94 mmol). The reaction was stirred RT for 16 h, and then solvent was removed under reduced pressure. The product was purified by column chromatography (5:1; hexanes:EtOAc) to give 431 mg of a solid (87%): Mp 92.0-94.0° C.; 1H NMR (CDCl3) δ 12.30 (s, 1H), 8.64 (s, 1H), 5.30 (t, 1H, J=6.0 Hz), 4.25 (t, 2H, J=6.4 Hz), 3.29 (q, 2H, J=6.0 Hz), 2.74 (s, 3H), 1.90-1.50 (m, 4H), 1.61 (s, 9H), 1.28 (bs, 20H), 0.88 (m, 6H). MS (EI): 525.1 (m+). 3-Methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.2) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with octyl isocyanate (3.83 mL, 3.37 g, 21.7 mmol) afforded 3.42 g of a solid (38%) after column chromatography (9:1; hexanes:EtOAc): Mp 119.0-120.0° C.; 1H NMR (CDCl3) δ 11.03 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.03 (vt, 1H), 3.29 (q, 2H, J=6.6 Hz), 2.71 (s, 3H), 1.63-1.40 (m, 2H), 1.57 (s, 9H), 1.26 (bs, 10H), 0.87 (t, 3H, J=6.6 Hz). MS (EI): 502.8 (m+). 3-Methyl-5-(3-tetradecyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.3) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with tetradecyl isocyanate (0.33 mL, 287 mg, 1.2 mmol) afforded 253 mg of a solid (36%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.5-106.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 22H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 587.1 (m+). 5-(3-Hexadecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.4) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with hexadecyl isocyanate (0.37 mL, 321 mg, 1.2 mmol) afforded 218 mg of a solid (30%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.0-105.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 26H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 615.1 (m+). 5-(3-Dodecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.5) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with decyl isocyanate (0.29 mL, 254 mg, 1.2 mmol) afforded 265 mg of a solid (40%) after column chromatography (9:1; hexanes:EtOAc): Mp 106.8-108.0° C.). 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.45-7.26 (m, 5H), 5.27 (s, 2H), 5.24 (t, 1H, J=5.6 Hz), 3.28 (q, 2H, J=6.6 Hz), 2.72 (s, 3H), 1.60-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 18H), 0.88 (t, 3H, J=6.4 Hz). MS (EI): 559.0 (m+).

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

Procedure: 295 g of a mixture of hexadecylisocyanate and octadecylisocyanate (commercial stearylisocyanate, 14.8% NCO) are slowly added to 159 g (1 mol) of 2-(2-isopropyl-1,3-oxazolidin-3-yl)-ethanol and 0.1 g of Sn(II) octoate at room temperature with stirring. Stirring is continued for 5 hours at about 50° C after all the isocyanate has been added. The product solidifies after some time to a waxy mass which melts to a clear liquid at temperatures of from 65° to 70° C. Stirring melts to a clear liquid at temperatures of from 65° to 70° C.

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

Procedure: 0.5 g of 2-methylamino-ethanol-phosphocholine is dissolved in 10 ml of N-methylacetamide; the solution is mixed with 1.08 g of hexadecyl-isocyanate and stirred for 24 hours at room temperature. The solution is reduced in vacuo and the residue purified by column chromatography (silica gel//chloroform/methanol/water). the residue purified by column chromatography (silica gel//chloroform/methanol/water)

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

Procedure: 1.34 ml (5 meq) of hexadecyl isocyanate and 0.7 ml (5 meq) of 3-dimethylaminopropylamine are combined in 5 ml of tetrahydrofuran and reacted over a weekend at room temperature. The reaction mixture is filtered, washed with tetrahydrofuran, dried in vacuo and recrystallized from acetone to yield 1.2 gm of title compound with a m.p. of 78°-79° C. reacted over a weekend at room temperature The reaction mixture is filtered washed with tetrahydrofuran dried in vacuo recrystallized from acetone