amino(trimethyl)azanium;iodide

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

Procedure: Compound 477A (0.438 g, 2.67 mmol) was dissolved in 25 mL of DMSO and trimethylhydrazinium iodide (0.534 g, 2.67 mmol) was added. Sodium pentoxide (0.880 g, 8.01 mmol) was added under N2 to give a deep red solution and stirring was continued overnight at rt. The reaction mixture was poured into 50 mL of 10% HCl and extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL), dried over sodium sulfate and concentrated in vacuo to give compound 477B as an oily red solid which was used directly in the next reaction without further purification. to give a deep red solution extracted with EtOAc (2×25 mL) The combined organic layers were washed with water (25 mL), brine (25 mL) dried over sodium sulfate concentrated in vacuo

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

Procedure: To a solution of 2-methyl-8-nitroquinoline (1.88 g, 10 mmol) and 1,1,1-trimethylhydrazinium iodide (3.03 g, 15 mmol) in anhydrous dimethyl sulfoxide (20 mL) was added potassium tert-butoxide as a solid (3.36 g, 30 mmol). The mixture was stirred at room temperature for 1 h. The mixture was then poured into saturated aqueous ammonium chloride, and extracted with EtOAc. The organic layer was concentrated and purified by column chromatography to give 2-methyl-8-nitroquinolin-7-amine as a yellow solid (300 mg). extracted with EtOAc The organic layer was concentrated purified by column chromatography

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

Procedure: To a solution of 2-methyl-8-nitroquinoline (1.88 g, 10 mmol) and 1,1,1-trimethylhydrazinium iodide (3.03 g, 15 mmol) in anhydrous dimethyl sulfoxide (20 mL) was added potassium tert-butoxide as a solid (3.36 g, 30 mmol). The mixture was stirred at room temperature for 1 h. The mixture was then poured into saturated aqueous ammonium chloride, and extracted with EtOAc. The organic layer was concentrated and purified by column chromatography to give 2-methyl-8-nitroquinolin-7-amine as a yellow solid (300 mg). extracted with EtOAc The organic layer was concentrated purified by column chromatography

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

Procedure: To a solution of 2-hydroxy-4-nitro-benzonitrile [1.0 g, 6.1 mmol, prepared as described in Yasubiro Imakura et. al. Chem. Pharm. Bull. 40 (7), 1691-1696 (1992)] in DMSO (60 mL) was added trimethylhydrazinium iodide (1.23 g, 6.09 mmol), followed by sodium tert-pentoxide (2.01 g, 6.09 mmol). The mixture was stirred at rt overnight, and then partitioned between 10% HCl and ether. The separated ether layer was washed with H2O, brine, dried (Na2SO4), and concentrated under reduced pressure to furnish the title compound (0.78 g) as a brown solid. partitioned between 10% HCl and ether The separated ether layer was washed with H2O, brine dried (Na2SO4) concentrated under reduced pressure

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

Procedure: Compound 477A (0.438 g, 2.67 mmol) was dissolved in 25 mL of DMSO and trimethylhydrazinium iodide (0.534 g, 2.67 mmol) was added. Sodium pentoxide (0.880 g, 8.01 mmol) was added under N2 to give a deep red solution and stirring was continued overnight at rt. The reaction mixture was poured into 50 mL of 10% HCl and extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL), dried over sodium sulfate and concentrated in vacuo to give compound 477B as an oily red solid which was used directly in the next reaction without further purification. to give a deep red solution extracted with EtOAc (2×25 mL) The combined organic layers were washed with water (25 mL), brine (25 mL) dried over sodium sulfate concentrated in vacuo

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

Procedure: Compound 477A (0.438 g, 2.67 mmol) was dissolved in 25 mL of DMSO and trimethylhydrazinium iodide (0.534 g, 2.67 mmol) was added. Sodium pentoxide (0.880 g, 8.01 mmol) was added under N2 to give a deep red solution and stirring was continued overnight at rt. The reaction mixture was poured into 50 mL of 10% HCl and extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL), dried over sodium sulfate and concentrated in vacuo to give compound 477B as an oily red solid which was used directly in the next reaction without further purification. to give a deep red solution extracted with EtOAc (2×25 mL) The combined organic layers were washed with water (25 mL), brine (25 mL) dried over sodium sulfate concentrated in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,1,1-trimethylhydrazinium iodide (14.7 g, 72.7 mmol) was added to potassium tert-butoxide (8.20 g, 72.7 mmol) and copper (I) chloride (0.180 g, 1.82 mmol) in DMF (50 mL) at 0° C. The resulting mixture was allowed to stir for several minutes at which point the mixture was cooled to −40° C. and 1-bromo-2,5-dichloro-3-(2-chloro-6-nitrophenoxy)benzene (7.23 g, 18.2 mmol) as a solution in DMF (50 mL) was added dropwise. The reaction mixture was then maintained at −40° C. for 20 minutes, at which point the reaction was quenched at −40° C. with saturated aqueous ammonium chloride (10 mL). Water (10 mL) was then added and the mixture was allowed to warm to room temperature. The mixture was extracted with ethyl acetate (2×200 mL). The combined organic fractions were washed with water (3×200 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by automated column chromatography on silica gel (1.5 kg) eluting with 25% EtOAc/hexanes to give the title compound. LRMS (M+1)=412.4. The reaction mixture was then maintained at −40° C. for 20 minutes, at which was quenched at −40° C. with saturated aqueous ammonium chloride (10 mL) Water (10 mL) was then added to warm to room temperature The mixture was extracted with ethyl acetate (2×200 mL) The combined organic fractions were washed with water (3×200 mL) dried (MgSO4) filtered the solvent was evaporated under reduced pressure The resulting residue was purified by automated column chromatography on silica gel (1.5 kg) eluting with 25% EtOAc/hexanes

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To copper (I) chloride (5.45 mg, 0.055 mmol) and potassium tert-butoxide (247 mg, 2.204 mmol) suspended in DMF (3 mL) at 0° C. was added 1,1,1-trimethylhydrazinium iodide (139 mg, 0.689 mmol). This mixture was allowed to stir for several minutes at which point the mixture was cooled to −40° C. and 2-(3-bromo-5-chlorophenoxy)-1-chloro-3-nitrobenzene (200 mg, 0.551 mmol) as a solution in DMF (1 mL) was added dropwise. The reaction was maintained at −40° C. for 15 minutes and was then quenched at −40° C. with saturated aqueous ammonium chloride (10 mL). Water (10 mL) was added and the mixture was allowed to warm to room temperature. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic fractions were washed with water (3×50 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by automated column chromatography on silica gel (40 g) eluting with 0-25% EtOAc/hexanes to give the title product. LRMS (M+1)=378.7. The reaction was maintained at −40° C. for 15 minutes was then quenched at −40° C. with saturated aqueous ammonium chloride (10 mL) Water (10 mL) was added to warm to room temperature The mixture was extracted with ethyl acetate (2×50 mL) The combined organic fractions were washed with water (3×50 mL) dried (MgSO4) filtered the solvent was evaporated under reduced pressure The resulting residue was purified by automated column chromatography on silica gel (40 g) eluting with 0-25% EtOAc/hexanes

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To copper (I) chloride (5.45 mg, 0.055 mmol) and potassium tert-butoxide (247 mg, 2.204 mmol) suspended in DMF (3 mL) at 0° C. was added 1,1,1-trimethylhydrazinium iodide (139 mg, 0.689 mmol). This mixture was allowed to stir for several minutes at which point the mixture was cooled to −40° C. and 2-(3-bromo-5-chlorophenoxy)-1-chloro-3-nitrobenzene (200 mg, 0.551 mmol) as a solution in DMF (1 mL) was added dropwise. The reaction was maintained at −40° C. for 15 minutes and was then quenched at −40° C. with saturated aqueous ammonium chloride (10 mL). Water (10 mL) was added and the mixture was allowed to warm to room temperature. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic fractions were washed with water (3×50 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by automated column chromatography on silica gel (40 g) eluting with 0-25% EtOAc/hexanes to give the title product. LRMS (M+1)=378.7. The reaction was maintained at −40° C. for 15 minutes was then quenched at −40° C. with saturated aqueous ammonium chloride (10 mL) Water (10 mL) was added to warm to room temperature The mixture was extracted with ethyl acetate (2×50 mL) The combined organic fractions were washed with water (3×50 mL) dried (MgSO4) filtered the solvent was evaporated under reduced pressure The resulting residue was purified by automated column chromatography on silica gel (40 g) eluting with 0-25% EtOAc/hexanes

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

Procedure: To a solution of 2-hydroxy-4-nitro-benzonitrile [1.0 g, 6.1 mmol, prepared as described in Yasubiro Imakura et. al. Chem. Pharm. Bull. 40 (7), 1691-1696 (1992)] in DMSO (60 mL) was added trimethylhydrazinium iodide (1.23 g, 6.09 mmol), followed by sodium tert-pentoxide (2.01 g, 6.09 mmol). The mixture was stirred at rt overnight, and then partitioned between 10% HCl and ether. The separated ether layer was washed with H2O, brine, dried (Na2SO4), and concentrated under reduced pressure to furnish the title compound (0.78 g) as a brown solid. partitioned between 10% HCl and ether The separated ether layer was washed with H2O, brine dried (Na2SO4) concentrated under reduced pressure

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

Procedure: Compound 477A (0.438 g, 2.67 mmol) was dissolved in 25 mL of DMSO and trimethylhydrazinium iodide (0.534 g, 2.67 mmol) was added. Sodium pentoxide (0.880 g, 8.01 mmol) was added under N2 to give a deep red solution and stirring was continued overnight at rt. The reaction mixture was poured into 50 mL of 10% HCl and extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL), dried over sodium sulfate and concentrated in vacuo to give compound 477B as an oily red solid which was used directly in the next reaction without further purification. to give a deep red solution extracted with EtOAc (2×25 mL) The combined organic layers were washed with water (25 mL), brine (25 mL) dried over sodium sulfate concentrated in vacuo

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

Procedure: Compound 477A (0.438 g, 2.67 mmol) was dissolved in 25 mL of DMSO and trimethylhydrazinium iodide (0.534 g, 2.67 mmol) was added. Sodium pentoxide (0.880 g, 8.01 mmol) was added under N2 to give a deep red solution and stirring was continued overnight at rt. The reaction mixture was poured into 50 mL of 10% HCl and extracted with EtOAc (2×25 mL). The combined organic layers were washed with water (25 mL), brine (25 mL), dried over sodium sulfate and concentrated in vacuo to give compound 477B as an oily red solid which was used directly in the next reaction without further purification. to give a deep red solution extracted with EtOAc (2×25 mL) The combined organic layers were washed with water (25 mL), brine (25 mL) dried over sodium sulfate concentrated in vacuo