heptanehydrazide

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

Procedure: Then, in a 50 ml-three-necked flask, 0.32 g (2.22 mM) of heptanohydrazide and 15 ml of dioxane were placed. To the mixture, a solution of the above-prepared 7-octyl-2-fluorenecarbonyl chloride in 5 ml of dioxane was added, followed by addition of 0.84 ml of pyridine at about 85° C. under stirring and further stirring for 30 minutes at 85°-88° C. After the reaction, the reaction mixture was cooled and poured into 200 ml of ice water to precipitate a crystal. The crystal was recrystallized from a mixture solvent of toluene-acetone to obtain 0.68 g of N-heptanoyl-N'-(7-octyl-2-fluorenecarbonyl) hydrazine (Yield: 69.8%). further stirring for 30 minutes at 85°-88° C After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recrystallized from a mixture solvent of toluene-acetone

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

Procedure: Then, in a 50 ml-three-necked flask, 0.32 g (2.22 mM) of heptanohydrazide and 15 ml of dioxane were placed. To the mixture, a solution of the above-prepared 7-octyl-2-fluorenecarbonyl chloride in 5 ml of dioxane was added, followed by addition of 0.84 ml of pyridine at about 85° C. under stirring and further stirring for 30 minutes at 85°-88° C. After the reaction, the reaction mixture was cooled and poured into 200 ml of ice water to precipitate a crystal. The crystal was recrystallized from a mixture solvent of toluene-acetone to obtain 0.68 g of N-heptanoyl-N'-(7-octyl-2-fluorenecarbonyl) hydrazine (Yield: 69.8%). further stirring for 30 minutes at 85°-88° C After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recrystallized from a mixture solvent of toluene-acetone

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

Procedure: Then, in a 50 ml-three-necked flask, 0.32 g (2.22 mM) of heptanohydrazide and 15 ml of dioxane were placed. To the mixture, a solution of the above-prepared 7-octyl-2-fluorenecarbonyl chloride in 5 ml of dioxane was added, followed by addition of 0.84 ml of pyridine at about 85° C. under stirring and further stirring for 30 minutes at 85°-88° C. After the reaction, the reaction mixture was cooled and poured into 200 ml of ice water to precipitate a crystal. The crystal was recrystallized from a mixture solvent of toluene-acetone to obtain 0.68 g of N-heptanoyl-N'-(7-octyl-2-fluorenecarbonyl) hydrazine (Yield: 69.8%). further stirring for 30 minutes at 85°-88° C After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recrystallized from a mixture solvent of toluene-acetone

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

Procedure: The title compound was prepared as a yellow solid, using isatin 3 and hexanecarbohydrazide according to the synthetic method E. The resulting solid was washed with ethanol. Yield: 32%. 1H NMR (DMSO-d6): δ 0.82-0.91 (m, 6H), 1.27-1.33 (m, 10H), 1.62 (m, 4H), 2.71 (br s, 1H), 3.74 (t, J=7.2 Hz, 2H), 7.15 (t, J=7.5 Hz, 1H), 7.19 (d, J=7.8 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 12.44 (br s, 1 H). 13C NMR (DMSO-d6): δ 14.25 (CH3), 14.29 (CH3), 22.30 (CH2), 22.42 (CH2), 26.33 (CH2), 27.36 (CH2), 31.26 (CH2), 31.28 (CH2), 39.59 (CH2), 110.46 (CH), 119.72 (C), 120.62 (CH), 123.41 (CH), 131.73 (CH), 143.22 (C═N), 161.01 (C═O). HRMS (ES+) calcd for C20H30N3O2 (M+H+), m/e, 344.2335; found, 344.2333. The resulting solid was washed with ethanol

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

Procedure: Prepared using General Procedure 7. Into a stirring solution of (S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid (50 mg, 0.10 mmol) in DCM (2 mL) were added EDC (34 mg, 0.20 mmol), DMAP (3 mg, 0.02 mmol) and heptanehydrazide (16 mg, 0.11 mmol). After 18 h, the reaction mixture was diluted with NaHCO3 and extracted with DCM (2×). The organic layers were combined, dried (Na2SO4), concentrated and purified by chromatography (EA/Hexane) to provide 38 mg (61%) of tert-butyl (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(2-heptanoylhydrazine-1-carbonyl)pyrimidin-2-yl)phenyl)propanoate. LCMS-ESI (m/z) calculated for C36H47BN5O5: 629.8; no m/z observed, tR=3.84 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 2H), 8.42 (d, J=8.2 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.2 Hz, 2H), 6.70 (d, J=7.3 Hz, 1H), 5.01 (dd, J=12.6, 5.8 Hz, 1H), 3.41-3.20 (m, 2H), 2.35 (t, J=7.5 Hz, 2H), 1.81-1.61 (m, 2H), 1.59 (d, J=14.0 Hz, 2H), 1.45 (s, 4H), 1.42-1.22 (m, 18H), 0.88 (t, J=6.8 Hz, 3H). Prepared extracted with DCM (2×) dried (Na2SO4) concentrated purified by chromatography (EA/Hexane)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 200 ml-three-necked flask, 1.77 g (12.3 mM) of heptanohydrazide, 3,23 g (13.0 mM) of 6-acetoxy-2-naphthoyl chloride prepared in the same manner as in Example 3 and 90 ml of dioxane were placed and heated to about 80° C. To the mixture, 5.0 ml of pyridine was added at about 80° C. under stirring, followed by heating to 90°-92° C. and stirring for 1 hour at 90°-92° C. After the reaction, the reaction mixture was cooled on an iced water bath and poured into 350 ml of iced water to precipitate a crystal. The crystal was recovered by filtration, followed by washing with water and recrystallization from a mixture solvent (acetoneethyl acetate) to obtain 3.23 g of N-heptanoyl-N'-(6-acetoxy-2-naphthoyl)hydrazine (Yield: 75.4 %) ##STR137## by heating to 90°-92° C. stirring for 1 hour at 90°-92° C After the reaction the reaction mixture was cooled on an iced water bath to precipitate a crystal The crystal was recovered by filtration by washing with water and recrystallization from a mixture solvent (acetoneethyl acetate)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 50 ml-three-necked flask, 0.40 g (2.77 mM) of heptanohydrazide, 1.05 g (3.03 mM) of 6-decyloxy-2-naphthoyl chloride and 20 ml of dioxane were placed and heated to about 85° C. under stirring. To the mixture, 1.05 ml (13.0 mM) of pyridine was added, followed by heating to 90°-92° C. and stirring for 40 minutes at 90°-92° C. After the reaction, the reaction mixture was cooled and poured into 150 ml of iced water to precipitate a crystal. The crystal was recovered by filtration, followed by washing with water and further washing with acetone to obtain 1.21 g of N-heptanoyl-N'-(6-decyloxy-2-naphthoyl)hydrazine (Yield: 96.0%). ##STR28## by heating to 90°-92° C. stirring for 40 minutes at 90°-92° C After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recovered by filtration by washing with water further washing with acetone

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

Procedure: The title compound was prepared as a yellow solid, using isatin 3 and hexanecarbohydrazide according to the synthetic method E. The resulting solid was washed with ethanol. Yield: 32%. 1H NMR (DMSO-d6): δ 0.82-0.91 (m, 6H), 1.27-1.33 (m, 10H), 1.62 (m, 4H), 2.71 (br s, 1H), 3.74 (t, J=7.2 Hz, 2H), 7.15 (t, J=7.5 Hz, 1H), 7.19 (d, J=7.8 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 12.44 (br s, 1H). 13C NMR (DMSO-d6): δ 14.25 (CH3), 14.29 (CH3), 22.30 (CH2), 22.42 (CH2), 26.33 (CH2), 27.36 (CH2), 31.26 (CH2), 31.28 (CH2), 39.59 (CH2), 110.46 (CH), 119.72 (C), 120.62 (CH), 123.41 (CH), 131.73 (CH), 143.22 (C═N), 161.01 (C═O). HRMS (ES+) calcd for C20H30N3O2 (M+H+), m/e, 344.2335. found, 344.2333. The resulting solid was washed with ethanol

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

Procedure: 12.2 g of hydrazine hydrate was added to a solution of 15 g of ethyl heptanoate in 20 ml of ethanol, followed by heat-refluxing for 4.5 hours. After the reaction, the reaction mixture was cooled to precipitate a crystal. The crystal was recovered by filtration and recrystallized from 20 ml of ethanol to obtain 7 g of heptanohydrazide. by heat-refluxing for 4.5 hours After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recovered by filtration recrystallized from 20 ml of ethanol

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

Procedure: Then, in a 50 ml-three-necked flask, 0.32 g (2.22 mM) of heptanohydrazide and 15 ml of dioxane were placed. To the mixture, a solution of the above-prepared 7-octyl-2-fluorenecarbonyl chloride in 5 ml of dioxane was added, followed by addition of 0.84 ml of pyridine at about 85° C. under stirring and further stirring for 30 minutes at 85°-88° C. After the reaction, the reaction mixture was cooled and poured into 200 ml of ice water to precipitate a crystal. The crystal was recrystallized from a mixture solvent of toluene-acetone to obtain 0.68 g of N-heptanoyl-N'-(7-octyl-2-fluorenecarbonyl) hydrazine (Yield: 69.8%). further stirring for 30 minutes at 85°-88° C After the reaction the reaction mixture was cooled to precipitate a crystal The crystal was recrystallized from a mixture solvent of toluene-acetone