4-Bromo-2-pyridinecarboxamide

yellow powder

third step:Add water to the 50 liter reactor, sodium hydroxide, stir to reduce the temperature to 0 , add bromine, drop the temperature to minus 10 degrees.Add the amide in batches and stir for one hour.Then heat to 80 degrees for one hour.The TCL was detected until the end of the reaction, and the temperature was lowered to room temperature and centrifuged to obtain a crude product which was crystallized from toluene to give a pure product of 1.5 kg.The ratio of each raw material in the third step of and the reaction conditions of the third step and the purity and yield of the obtained product are shown in Table 2.The second step: 8.5 kg of A was added to 35 liters of ammonia water in batches, methane was stirred overnight, and centrifuged to obtain a crude product which was washed with ethyl acetate and centrifuged to obtain 4.5 kg of amide;A mixture of compound 53 (188 mg, 0.37 mmol), EXAMPLE 64-((4-Oxo-3-o-tolyl-3, 4-dihydropyrrolo[1 , 2-tf[1 , 2, 4]triazin-2- yl)methylamino)picolinamideA mixture of 2-(aminomethyl)-3-o-tolylpyrrolo[1 , 2-7[1 .2, 4]triazin-4(3H)-one (102 mg, 0.4 mmol), EXAMPLE 6 4-((4-Oxo-3-o-tolyl-3, 4-dihydropyrrolo[1, 2-f][1, 2, 4]triazin-2-yl)methylamino)picolinamide A mixture of 2-(aminomethyl)-3-o-tolylpyrrolo[1, 2-f][1, 2, 4]triazin-4(3H)-one (102 mg, 04 mmol), (ii) (S)-tert- uty l-(2-(4-(2-carbamoylpyridin-4-yl)phcyanoethylcarbamoyl)cyclohexylcarbamateA solution of (S)-tert-butyl l-(l-cyano-2-(4-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2- yl)phenyl)ethylcarbamoyl)cyclohexylcarbamate (Example 23 step (i), 569 mg), potassium acetate (225 mg) and The flask was charged with (2-(2-chlorophenyl)-8-methylquinolin-3-yl)methan- amine (100.0 mg, 0.354 mmol), obtained from A-1216 US PSP, procedure D, 4- bromopicolinamide (92 mg, 0.460 mmol), diisopropylethylamine (0.080 ml, 0.460 mmol) and 1-butanol (2.0 ml ) and sealed. The mixture was subjected to microwave at 180C for 4hrs. After cooled to room temperature, the mixture was concentrated, and the residue was diluted with MeOH. The solution was purified by HPLC, 25%-45% of B in 35min. The collected fractions were concentrated and dissolved in CH2Cl2, neutralized by washing with aq. NaHCO3. The CH2Cl2 layer was dried, concentrated and gave 4-((2-(2-chlorophenyl)-8-methylquinolin- 3-yl)methylamino)picolinamide, 1H-NMR (MeOD) delta 8.21 (s, 1 H), 8.01(d, J= 5.6 Hz, IH), 7.71 (d, J= 8.0 Hz, IH), 7.41-7.62 (m, 6 H), 7.20 (d, J= 2.4 Hz, IH), 6.50 (dd, J= 5.6, 2.4 Hz, IH) 4.42 (d, J= 11.0 Hz, IH), 4.27 (d, J= 11.0 Hz, IH), 2.73 (s, 1 H). Mass Spectrum (ESI) m/e = 403.1 (M + 1).

Molecular Weight:201.02
XLogP3:0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:199.95853
Monoisotopic Mass:199.95853
Topological Polar Surface Area:56
Heavy Atom Count:10
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes