1-(4-AMINO-PHENYL)-1H-PYRIDIN-2-ONE

In a 100 mL round bottle, 1-(4-nitrophenyl)pyridin-2(1H)-one (1.0 g, 4.63 mmol, Eq: 1.00) and zinc (1.51 g, 23.1 mmol, Eq: 5.00) were combined with a solution of saturated NH4Cl aqueous solution/ THF (1:1) (50 ml), the mixture was stirred at for overnight. Filter out the solid, extracted with CH2Ch (50 mLx2), the organic layer was dried over anhydrous Na2S04; the solution was concentrated under vacuum to afford the crude product 740 mg (86percent). MH+ 188.3Synthesis of 1-(4-Amino-phenyl)-1H-pyridin-2-one In a 3000L reactor, iodoaniline 438kg, 2-hydroxypyridine 190kg, 8-hydroxyquinoline 58kg, potassium carbonate 207kg, N, N-dimethylformamide (DMF) 1500kg, nitrogen protection, stirring is turned on. The mixture was warmed to reflux and reacted overnight. Chromatography was followed up to the end of the reaction. The potassium iodide was removed by filtration. Part of the DMF was recovered under reduced pressure, cooled to 50° C., and filtered to give crude 1-(4-aminophenyl)-1H-pyridin-2-one. The crude product was added with 740 kg of ethanol, heated and dissolved, and 55 kg of activated carbon was added for decoloration. The solution was filtered while hot, and the filtrate was cooled and crystallized. The product was filtered, dried and packaged to give 1-(4-aminophenyl)-1H-pyridin-2-one with a yield of 95. percent, The purity is 99percent.11128] In a similar manner as described in Example 114, (R)-5-(3-(4-methoxybenzamido)piperidin- 1 -yl)-3-(4-(2-ox-opyridin- 1 (2H)-yl)phenylamino)pyrazine-2-carboxamide(154) was prepared using 1 -(4-aminophenyl)pyridin-2(1H)-one. MS found for C29H29N704 as (M+H) 540.1, (M—H)538.3. UV: X=260, 285, 308, 346, 369 nm Synthesis of i-(4-aminophenyl)pyridin-2(1H)-one: The mixture of 4-iodoa-niline (1.00 g, 4.56 mmol), 2-hydroxypyridine (650 mg, 6.84mmol), fine powder Cs2CO3 (2.97 g, 9.12 mmol), fine powderCul (180mg, 0.92 mmol), 8-hydroxyquinoline (140mg, 0.92mmol) in 6 mE DMSO and 10 mE dioxane was stirred in asealed tube at 120° C. for 15 h. The mixture was diluted with300 mE EtOAc, filtered through celite, washed with brine, dried, concentrated and subjected to flash column with 0 to7percent MeOR in dichioromethane to isolate this compound (590mg, yield 70percent).General procedure: Compound 1 (5g, 22.83mmol) was dissolved in DMSO (120mL), followed by the addition of 2-Piperidinone (4.53g, 45.66mmol), CuI (0.43g, 2.28mmol), 8-hydroxy-quinoline (0.66g, 4.57mmol) and KA mixture of pyridin-2-ol (2.00 g, 21.0 mmol), 4-iodoaniline (4.61 g, 21.0 mmol), 8-quinolinol (0.61 g, 4.2 mmol), Cul (0.80 g, 4.2 mmol) and CsA mixture of pyridin-2-ol (2.00 g, 21.0 mmol), 4-iodoaniline (4.61 g, 21.0 mmol), 8-quinolinol (0.61 g, 4.2 mmol), Cul (0.80 g, 4.2 mmol) and CsTo a solution of the oil (110 mg, 0.40 mmol), 4-(2-pyridon-l-yl)phenylamine (89 mg, 0.48 mmol) and triethylamine (170 uL, 1.22 mmol) in DMF (3 mL), BOP (229 mg, 0.52 mmol) was added. After being stirred at room temperature overnight, H2O and EtOAc were added. The organic phase was separated, washed with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give the desired carboxamide. The carboxamide was dissolved in TFA (4 mL). After being stirred for Ih, TFA was removed in vacuo. The residue was partitioned between EtOAc and 5% NaHCO3. The EtOAc phase was separated, dried over Na2SO4, concentrated in vacuo to give a solid (60 mg).

Molecular Weight:186.21
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:186.079312947
Monoisotopic Mass:186.079312947
Topological Polar Surface Area:46.3
Heavy Atom Count:14
Complexity:275
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes