4-bromoheptane

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: Using the general method of Compound 42 Part B, 4-bromoheptane (5.84 g, 32.6 mmole) was reacted with 1-benzyloxy-3-phenylurea (7.3 g, 30.2 mmole) to provide about 4 g of 1-benzyloxy-1-(1-propylbutyl)-3-phenylurea.

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

Procedure: Using the general method of Compound 42 Part B, 4-bromoheptane (5.84 g, 32.6 mmole) was reacted with 1-benzyloxy-3-phenylurea (7.3 g, 30.2 mmole) to provide about 4 g of 1-benzyloxy-1-(1-propylbutyl)-3-phenylurea.

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

Procedure: To a solution of the 4-[5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (120 mg, 0.30 mmol) in DMF (4 mL), NaH (60 wt % suspension in mineral oil, 36 mg, 0.89 mmol) is added followed by 4-bromoheptane (159 mg, 0.89 mmol). The mixture is stirred for 40 h at room temperature. The mixture is poured to water (10 mL), and the product is extracted with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Chromatography of the residue affords 4-[5-(2,6-diethyl-phenyl)-1-(1-propyl-butyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as colorless oil. the product is extracted with EtOAc The combined organic extracts are washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: To a solution of 5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridine (32 mg, 0.13 mmol) in DMF (0.5 mL) is added NaH (95%, 6 mg). The reaction mixture is stirred at room temperature for 30 minutes, and 4-bromo-heptane (137 mg, 0.77 mmol) is added. The mixture is heated at 60° C. for three hours and cooled. To the mixture, water (2 mL) and EtOAc (2 mL) are added. The organic layer is separated, washed with water once and concentrated under reduced pressure. The residue is purified by PTLC (Hexane/EtOAc 4:1) to give the titled compound. 1H NMR: (CDCl3) 8.82 (s, 1H), 7.43 (s, 1H), 7.32 (d, 1H), 7.31 (t, 1H), 7.16 (d, 2H), 6.87 (s, 1H), 6.53 (d, 1H), 4.42 (m, 1H), 2.32-2.40 (m, 4H), 1.86-1.95 (m, 4H), 1.15-1.32 (m, 4H), 1.03 (t, 6H), 0.84 (m, 6H). The mixture is heated at 60° C. for three hours cooled The organic layer is separated washed with water once concentrated under reduced pressure The residue is purified by PTLC (Hexane/EtOAc 4:1)

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

Procedure: To 0.041 g (0.16 mmol) of 5-(2,4-dimethylphenyl)-3-methylcinnolin-4(1H)-one in 0.5 mL of N-methylpyrrolidine was added 0.069 mL of 4-bromoheptane and 0.012 g (0.31 mmol) of sodium hydride (60% dispersion in mineral oil). The mixture was stirred for 75 min. at room temperature and quenched with water. The mixture was extracted with ethyl acetate and the combined organics were washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography eluting with a 8% ethyl acetate/hexanes mixture to give 0.042 g (75%) of the title compound as a light green-yellow semisolid. quenched with water The mixture was extracted with ethyl acetate the combined organics were washed with water and brine dried over sodium sulfate filtered concentrated The residue was purified by flash chromatography eluting with a 8% ethyl acetate/hexanes mixture

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

Procedure: To a solution of 8-(2,4-dimethylphenyl)-2-methyl-2H-1,4-benzoxazin-3(4H)-one (300 mg, 1.12 mmol) in N,N-dimethylformamide (5 ml) was added sodium hydride (43 mg, 1.68 mmol). After the mixture was stirred at 80° C. for 30 min, 4-bromoheptane (804 mg, 4.49 mmol) was added. The mixture was stirred at 80° C. for 18 h and diluted with water. The aqueous solution was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography eluting with 5% ethyl acetate/n-hexane to afford 186 mg (30%) of the title compound. The mixture was stirred at 80° C. for 18 h The aqueous solution was extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate concentrated under vacuum The residue was purified by column chromatography eluting with 5% ethyl acetate/n-hexane

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

Procedure: To a solution of the 4-[5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (120 mg, 0.30 mmol) in DMF (4 mL), NaH (60 wt % suspension in mineral oil, 36 mg, 0.89 mmol) is added followed by 4-bromoheptane (159 mg, 0.89 mmol). The mixture is stirred for 40 h at room temperature. The mixture is poured to water (10 mL), and the product is extracted with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Chromatography of the residue affords 4-[5-(2,6-diethyl-phenyl)-1-(1-propyl-butyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as colorless oil. the product is extracted with EtOAc The combined organic extracts are washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: To a solution of the 4-[5-(2,6-diethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (120 mg, 0.30 mmol) in DMF (4 mL), NaH (60 wt % suspension in mineral oil, 36 mg, 0.89 mmol) is added followed by 4-bromoheptane (159 mg, 0.89 mmol). The mixture is stirred for 40 h at room temperature. The mixture is poured to water (10 mL), and the product is extracted with EtOAc. The combined organic extracts are washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Chromatography of the residue affords 4-[5-(2,6-diethyl-phenyl)-1-(1-propyl-butyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as colorless oil. the product is extracted with EtOAc The combined organic extracts are washed with brine dried over Na2SO4 concentrated under reduced pressure