3-PYRIDINAMINE, 6-(1-METHYLETHYL)-

2-Isopropyl-5-nitro-pyridine (1.30 g, 7.82 mmol) was dissolved in methyl alcohol (20 mL), and Raney Ni (0.25 g) was added. The mixture was stirred under H3. Preparation of 5-amino-2-isopropylpyridine100 g (0.41 mol) of 5-(Boc-amino)-2-isopropylpyridine are slurried up at room temperature in 500 g (8.3 mol) of isopropanol. Then, 200 g (1.8 mol) of an approximately 33percent solution of hydrogen chloride in isopropanol are metered at 25° C. On completion of the metered addition the batch is stirred at 25° C. for 30 min, then heated up to 50° C. over about 1 h and stirred at 50° C. for 3 h. Subsequently, 600 mL of distillate are removed under atmospheric pressure and 350 g (3.8 mol) of toluene are added to the resulting suspension at 40-50° C. The resulting suspension is discharged at room temperature onto a mixture of 150 g (8.3 mol) of completely ion-free water and 110 g (1.4 mol) of 50percent aqueous sodium hydroxide solution and stirred at room temperature for 15 mM. Following phase separation, the organic phase is concentrated in vacuo and the remaining oil is fractionally distilled through a column at 8 mbar.Yield: 47.7 g (0.35 mol, 85percent)Amixture of (S)-4-(2, 5-difluorophenyl)-2-(3-fluoropyrrolidin-1-yl)nicotinicacid (80.0 mg, 0.248 mmol), Amixture of (S)-3-(2, 5-difluorophenyl)-5-(3-fluoropyrrolidin-1-yl)isonicotinicacid (100 mg, 0.310 mmol), Amixture of 2-(4-chlorophenyl)-6-morpholino-benzoic acid (210 mg, 0.59 mmol, 90%purity calculated by LC-MS analysis), Toa mixture of 2-(4-chlorophenyl)-4-morpholinonicotinic acid (125 mg, 0.392 mmol)in THF (5 mL) was added (COCl)2 (199 mg, 1.57 mmol) and a drop ofDMF via syringe at 0 C. The reaction mixture was warm to room temperature andstirred for 4 h. The reaction mixturewas concentrated in vacuo and theresidue was dissolved in THF (8 mL). To the mixture were added Et3N(119 mg, 1.18 mmol) and Toa solution of 3-(4-chlorophenyl)-5-morpholinoisonicotinic acid (52.0 mg, 0.163 mmol) in THF (2 mL)was added (COCl)2 (41.4 mg, 0.326 mmol) and a drop of DMF viasyringe at 0 C. The reaction mixture was warm to room temperature and stirredfor 1 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in THF (2 mL). To themixture were added Et3N (49.5 mg, 0.495 mmol) andToa solution of 4-(4-chlorophenyl)-2-morpholinonicotinic acid (435 mg, 1.33 mmol, 98% purity calculated by LC-MS analysis) in THF (4 mL) was added (COCl)2(346 mg, 2.73 mmol) and a drop of DMF via syringe at 0 C. The reaction mixturewas warm to room temperature and stirred for 1 h. The reaction mixture was concentrated in vacuo and the residue was dissolvedin THF (4 mL). To the mixture were addedEt3N (414 mg, 4.09 mmol) and Step1: 4, 6-dichloro-N-(6-isopropylpyridin-3-yl)pyrimidine-5-carboxamideToa solution of 4, 6-dichloropyrimidine-5-carboxylic acid (CAS: 87600-98-4, commercially available, 1.49 g, 7.71 mmol) and a catalytic amount of DMF in anhydrous THF (15 mL) was added(COCl)2 (0.844 mL, 9.64 mmol) at 0 C. The mixture was stirred atroom temperature for 30 min. The mixture was directly concentrated in vacuo with toluene to give crude4, 6-dichloropyrimidine-5-carbonyl chloride as a yellow oil. To a solution ofthe above crude 4, 6-dichloropyrimidine-5-carbonyl chloride (7.71 mmol) in anhydrous THF (15 mL) was addeda solution of

Molecular Weight:136.19
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:136.100048391
Monoisotopic Mass:136.100048391
Topological Polar Surface Area:38.9
Heavy Atom Count:10
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes