N-(3-IODO-PYRIDIN-2-YL)-2,2-DIMETHYL-PROPIONAMIDE

A cold solution (-78° C.) of 2-pivaloylamino-pyridine (6a, 500 g, 2.8 mol) in tetrahydrofuran (6 L) was treated with n-butyllithium (2.5 M in hexanes, 2.25 L, 5.63 mol) at a rate such that the temperature did not exceed -55° C. The mixture was stirred for 1 hour until metallation was determined to be complete. A solution of iodine (782 g, 3.01 mol) in tetrahydrofuran (1 L) was added at a rate that the temperature did not exceed -65° C. Upon complete addition, the reaction was stirred for 2 hours and the reaction mixture was slowly poured into ice water (6 L). The mixture was diluted with ethyl acetate (6 L) and the layers separated. The aqueous was washed with ethyl acetate (4 L) and then the combined organics washed with a solution of sodium thiosulfate in water (200 g per liter, 3.x.4 L) followed by washing with aqueous saturated sodium chloride solution (2.x.4 L). The organics were dried over sodium sulfate and solvent removed under reduced pressure to yield 7a as a tan to brown solid of sufficient purity to take into the next step. Yield: 800 g, 94percent.N-(3-iodopyridin-2-yl)pivalamide Manufacturing Example 39-1-2 N-(3-Iodo-pyridin-2-yl)-2, 2-dimethyl-propionamide; To a mixture of 2, 2-dimethyl-N-pyridin-2-yl-propionamide (3.0 g, 17 mmol) described in Manufacturing Example 39-1-1, N, N, N', N'-tetramethylethylenediamine (6.3 mL, 42 mmol) and tetrahydrofuran (60 mL) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 30 mL, 47 mmol) at -78° C., which was stirred overnight at 0° C. Iodine (6.8 g, 27 mmol) was added to the reaction mixture at -78° C., and stirred for 1.5 hours at 0° C. Water and saturated aqueous sodium thiosulfate solution were added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (2.9 g, 57percent).To a mixture of 2, 2-dimethyl-N-pyridin-2-yl-propionamide (3.0 g, 17 mmol) described in Manufacturing Example 39-1-1, N, N, N', N'-tetramethylethylenediamine (6.3 mL, 42 mmol) and tetrahydrofuran (60 mL) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 30 mL, 47 mmol) at -78° C., which was stirred overnight at 0° C. Iodine (6.8 g, 27 mmol) was added to the reaction mixture at -78° C., and stirred for 1.5 hours at 0° C. Water and saturated aqueous sodium thiosulfate solution were added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (2.9 g, 57percent). Manufacturing Example 1-2-2 Manufacturing Example 39-1-3 N-(3-(4-Bromo-pyrazol-1-yl)-pyridin-2-yl)-2, 2-dimethyl-propionamide; To a mixture of To a mixture of

Molecular Weight:304.13
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:304.00726
Monoisotopic Mass:304.00726
Topological Polar Surface Area:42
Heavy Atom Count:14
Complexity:213
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes