(3-chlorophenyl)hydrazine;hydrochloride

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

Procedure: 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.).

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

Procedure: 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

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

Procedure: (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

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

Procedure: 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).

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

Procedure: 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).

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

Procedure: 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.

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

Procedure: 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.

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

Procedure: 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.

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

Procedure: 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.

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

Procedure: 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

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

Procedure: 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

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

Procedure: 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