(3-chlorophenyl)hydrazine;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Similar to Example 1, equimolar amounts of 3-chlorophenylhydrazine hydrochloride and 2-acetyl-3-oxo-butyric acid ethyl ester were combined in a solution of 50% pyridine in ethanol. Analysis confirmed that the resulting solid was determined to be the named product (m.p. 56° C.-57° C.).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 12.0 g (0.112 mol) of sodium carbonate suspended in 50 mL THF was added 5.0 g (0.028 mol) 3-chlorophenyl hydrazine hydrochloride, 6.5 g (0.033 mol) ethyl bromopyruvate and 44.0 g (0.42 mol) styrene. The reaction mixture was stirred at room temperature for 18 h, filtered through a plug of celite, rinsed with methylene chloride and concentrated under reduced pressure. The crude reaction mixture was flash chromatographed using 10% EtOAc/90% hexanes as eluent to afford 3.2 g of a yellow solid, mp 125°-126° C. filtered through a plug of celite rinsed with methylene chloride concentrated under reduced pressure The crude reaction mixture chromatographed

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (see, e.g., Ganesan, A., et al., Journal of Organic Chemistry 1993, 58, 6155-6157). A solution of 3-aminocrotonitrile (mixture of cis and trans) (1.50 g, 17.5 mmol) and 3-chlorophenylhydrazine hydrochloride (3.0 g, 16.2 mmol) in 25 mL of 1N HCl was heated to reflux for 3 h under nitrogen. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (20 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude was recrystallized from hot iPrOH to give the title compound (677 mg, 20%) as a beige fluffy solid. 1H NMR (500 MHz, CDCl3) δ 7.62 (s, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.37 (t, J=8.0 Hz, 1H), 7.28 (d, J=9.5 Hz, 1H), 5.46 (s, 1H), 2.22 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 149.95, 145.30, 139.87, 135.05, 130.32, 126.86, 123.67, 121.28, 91.41, 13.89. to reflux for 3 h under nitrogen extracted with EtOAc (20 mL×2) The combined organic layers were washed with brine dried (Na2SO4) filtered concentrated under reduced pressure The crude was recrystallized from hot iPrOH

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In analogy to the procedure described in Example 38A], 3-chlorophenylhydrazine hydrochloride and ethyl diacetoacetate gave the title compound after purification by flash column chromatography (n-heptane:EtOAc 9:1-1:1) in 58% yield as light yellow solid. MS: 279.0 (MH+, 1 Cl).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In analogy to the procedure described in Example 38A], 3-chlorophenylhydrazine hydrochloride and ethyl diacetoacetate gave the title compound after purification by flash column chromatography (n-heptane:EtOAc 9:1-1:1) in 58% yield as light yellow solid. MS: 279.0 (MH+, 1 Cl).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 560 mg (2.14 mmol) of the compound of Example 19A is reacted analogously to the synthesis of the compound of Example 20A with 422 mg (2.36 mmol) of 3-chlorophenylhydrazine hydrochloride. After hydrolysis, 494 mg (69% of theory) of the title compound is obtained.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 560 mg (2.14 mmol) of the compound of Example 19A is reacted analogously to the synthesis of the compound of Example 20A with 422 mg (2.36 mmol) of 3-chlorophenylhydrazine hydrochloride. After hydrolysis, 494 mg (69% of theory) of the title compound is obtained.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.13 g (3.25 mmol) of the compound of Example 18A is reacted analogously to the synthesis of the compound of Example 20A with 874 mg (4.88 mmol) of 3-chlorophenylhydrazine hydrochloride. After hydrolysis, 609 mg (49% of theory) of the title compound is obtained.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 mg (0.86 mmol) of the compound of Example 15A is reacted analogously to the synthesis of the compound of Example 20A with 230 mg (1.29 mmol) of 3-chlorophenylhydrazine hydrochloride. After hydrolysis, 21 mg (7% of theory) of the title compound is obtained.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound is prepared by following Method 8 by using 1-(2-bromoethyl)-4-fluorobenzene, 3-chlorophenylhydrazine hydrochloride, triethylamine and N-methyl-4-piperidone

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound is prepared by following Method 8 by using 1-(2-bromoethyl)-4-fluorobenzene, 3-chlorophenylhydrazine hydrochloride, triethylamine and N-methyl-4-piperidone

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound is prepared by following Method 8 by using 1-(2-bromoethyl)-4-fluorobenzene, 3-chlorophenylhydrazine hydrochloride, triethylamine and N-methyl-4-piperidone