2-Chloro-N-phenyl-isonicotinamide

To the sol. of 2-chloroisonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J Med Chem., 1990, 33, 1667, 10 g, 56.8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667, 10 g, 56.8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2CI2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.12-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C., Endo, T., J Med Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0. 87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C. , Endo, T., J Med. Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233. 1.General procedure: In a typical experiment, Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), 2, 5-diiodopyridine(331 mg, 1 mmol), 2, 3-diiodopyridine (331 mg, 1 mmol) or 2-chloro-3, 4-diiodopyridine (182.75 mg, 0.5 mmol), amine nucleophile (see above in the tables; 3 mmol of a/2 mmol of b/1.5 mmol of c, d/1.1 mmol of e, f, g, h) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL autoclave. The atmosphere was changed to carbon monoxide and the autoclave was pressurized to the given pressure by carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 50 C andanalysed by GC-MS (internal standard: naphthalene). The mixture was then concentrated and evaporated to dryness and worked-up as described in Section 4.2.To the sol. of 2-chloroisonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J Med Chem., 1990, 33, 1667, 10 g, 56.8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667, 10 g, 56.8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2CI2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.12-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K. , Dean, D. C. , Endo, T., J. Med. Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N) To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C., Endo, T., J Med Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2-dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2Cl2 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0. 87 min; ES+ = 233.1.2-Chloro-N-phenylisonicotinamide (N); To the sol. of 2-chloro-isonicotinoyl chloride (Anderson, W. K., Dean, D. C. , Endo, T., J Med. Chem., 1990, 33, 1667, 10 g, 56. 8 mmol) in 1, 2-dichloroethane (100 mL) was added at 0 °C a sol. of aniline (5.70 mL, 62.5 mmol) and DIPEA (10.2 ml, 59.6 mmol) in 1, 2- dichloroethane (10 ml) during ca. 30 min. The reaction was stirred at 0 °C for ca. 30 min and subsequently for 1 h at 95 °C. Water (30 mL) was added at rt and the mixture was filtered-off. The filtrate was extracted with CH2C12 (200 mL). The combined org. extracts were dried over MgS04, filtered, and the solvents were removed under reduced pressure. The residue was crystallized from MeOH/water 1: 10 (110 mL), yielding the title compound (12.12 g, 92percent). LC-MS: RT = 0.87 min; ES+ = 233. 1.General procedure: In a typical experiment, Pd(OAc)2 (5.6 mg, 0.025 mmol), triphenylphosphine (13.1 mg, 0.05 mmol), 2, 5-diiodopyridine(331 mg, 1 mmol), 2, 3-diiodopyridine (331 mg, 1 mmol) or 2-chloro-3, 4-diiodopyridine (182.75 mg, 0.5 mmol), amine nucleophile (see above in the tables; 3 mmol of a/2 mmol of b/1.5 mmol of c, d/1.1 mmol of e, f, g, h) and triethylamine (0.5 mL) were dissolved in DMF (10 mL) under argon in a 100 mL autoclave. The atmosphere was changed to carbon monoxide and the autoclave was pressurized to the given pressure by carbon monoxide. The reaction was conducted for the given reaction time upon stirring at 50 C andanalysed by GC-MS (internal standard: naphthalene). The mixture was then concentrated and evaporated to dryness and worked-up as described in Section 4.2.

Molecular Weight:232.66
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:232.0403406
Monoisotopic Mass:232.0403406
Topological Polar Surface Area:42
Heavy Atom Count:16
Complexity:241
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes