6-Methyl-5-nitro-2-pyridinamine

Light yellow Cryst

10 mL of concentrated sulfuric acid was cooled at 0-1 ° C, slowly adding raw material 1 (20 g), cooled to 0 ° C, slowly added 110 mL of nitric acid at a volume ratio of 1: 1, stirred at -1 ° C and stirred at room temperature for 30 min. Reaction was carried out at 50 ° C for 11 h. The reaction solution was extracted with EA. The EA layer was washed with aqueous ammonia and the aqueous ammonia was concentrated. The solid layer 2 (18 g) was precipitated and the yield was 75percent.Example 8 2-Methyl-2- (6-methyl-5-nitro-pyridin-2-ylamino)-propan-1-ol (a) Conc. H2S04 (140 ml) was cooled in an ice-salt bath and molten 6-amino-2-picoline (30 g, 0.277 mol) was added in portions with good stirring. To this brown, viscous solution which was maintained at 0°C was added a cooled (0°C) mixture of conc. H2SO4 (21 ml) and conc. HNO3 (21 ml) drop wise over a period of approx. 1.5 hrs. The red- orange reaction mixture was stirred for an additional hour at 0°C and then allowed to warm slowly to room temperature over night. The brown solution was heated at 60° C (oil bath) for 1 hr followed by lhr at 100°C (carefully controlled temperature). The reaction mixture was cooled to 0°C (ice bath), poured over cracked ice and neutralised by addition of a concentrated aqueous NaOH solution. The yellow precipitate was filtered and washed well with ice-water. (The filtrate was put in the refrigerator, additional product was precipitated together with the salts. ) The yellow product was suspended in water and divided into two portions, each of them subjected to steam distillation in turn. The yellow reaction mixture became more'transparent'after some hrs, but the collected steam, containing 4-amino-3-nitro-2-picoline, was still yellow after 6 hrs. The steam distillation was stopped after 8 hrs, the residual part of the reaction mixture was filtered and evaporated to dryness. 1HNMR (D2O) showed a mixture of 2-3 compounds. The mixture was washed with; CHCI ;, EtOH (x 2) and CHC leaving 20.4 g (48percent) of pure 6-amino- 3-nitro-2-picoline.The 6-methylpyridin-2-amine (20g, 185mmol) was dissolved in 98percent HGeneral procedure: 2-Fluoro-3-iodopyridine (1 mmol, 223.0 mg), acetamidine hydrochloride (1.2 mmol, 113.4 mg), NaOH (2.5 mmol, 100 mg), H2O (0.5 mL) and Dimethyl sulfoxide (2.5 mL). The reaction was carried out at 130 C for a reaction time of 24 hours. After the reaction was completed, it was cooled to room temperature.The reaction was quenched by adding 10 mL of ethyl acetate, and washed with 6 mL of saturated brine.The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate (6 mL of ethyl acetate each time). The organic phase was combined, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, including organic solvent and inorganic solvent. Organic solvent, The title product 3-iodopyridin-2-amine was isolated by column chromatography to give a yield of 95%.To a solution of 6-methyl-5-nitropyridin-2-amine (300 mg, 1 .959 mmol) in dichloromethane (DCM) (10 ml_) was added 2-(4-chlorophenoxy)acetyl chloride (402 mg, 1 .959 mmol) and TEA (0.819 ml_, 5.88 mmol). The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water (10 ml_). The resulting solution was extracted with dichloromethane (3 x 20 ml_) and the organic layers were combined, washed with brine (2 x20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford crude product. The crude product was purified by Prep-TLC. Mobile phase: 50% EtOAc/PE; Rf = 0.5 ; UV detection, to provide the title compound as a brown solid (400 mg, 95.8% pure, 63.5% yield).

Molecular Weight:153.14
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:153.053826475
Monoisotopic Mass:153.053826475
Topological Polar Surface Area:84.7
Heavy Atom Count:11
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes