PYRIMIDINE-4-CARBOXALDEHYDE

Procedure G: Intermediate 7 (1-7) - Pyrimidine-4-carboxaldehyde.; [0091] To a solution of 1.0 g (10 mmol, 1.0 eq.) of 4-methylpyrimidine in 10 mL of />-dioxane was added 1.2 g (10 mmol, 1.0 eq.) of selenium dioxide. The resulting mixture was heated at 100 c) Pyrimidine-4-carbaldehyde (C12)Procedure G: Intermediate 7 (1-7) - Pyrimidine-4-carboxaldehyde.; [0091] To a solution of 1.0 g (10 mmol, 1.0 eq.) of 4-methylpyrimidine in 10 mL of />-dioxane was added 1.2 g (10 mmol, 1.0 eq.) of selenium dioxide. The resulting mixture was heated at 100 0C for 5 h and then cooled to room temperature. After adding an additional 0.25 g (2.3 mmol, 0.23 eq.) of selenium dioxide, the reaction mixture was heated at 100 0C for a further 1 h. The mixture was cooled to room temperature and filtered through Celite. The Celite cake was washed with 200 mL of ethyl acetate and the filtrate was concentrated in vacuo. The resulting dark brown oil was suspended in 200 mL of methylene chloride and filtered. The solvent was removed in vacuo to afford 0.3 g (2.8 mmol, 28%) of pyrimidine-4-carboxaldehyde (1-7) as dark brown oil.EXAMPLE 147 Step A-Preparation of pyrimidine-4-yl formaldehyde Pyrimidine-4-yl formaldehyde was prepared from 4-methyl pyrimidine through a reference described in M. C. Liu et al., J Med Chem., 1995, 38 (21), 4234-4243.PREPARATION H 4-Formylpyrimidine A solution of 4-methylpyrimidine (10 g, 0.106 mole) in 100 ml dioxane was treated with 11.8 g selenium dioxide at room temperature and the mixture was heated at 100 C. for 15 hours. After adding 2.5 g selenium dioxide, heating was continued one hour, the mixture cooled, filtered, and the cake washed with ethyl acetate. The filtrate and washings were evaporated to dryness in vacuo . The residual dark oil was taken up in methylene chloride, filtered and the solvent evaporated. The residue was crystallized from a small amount of methylene chloride to provide the title aldehyde. 1H-NMR(CDCl3)ppm (delta): 7.87 (dd, 1H), 9.06 (d, 1H), 9.43 (d, 1H), 10.0 (s, 1H)PREPARATION H 4-Formylpyrimidine A solution of 4-methylpyrimidine (10 g, 0.106 mole) in 100 ml dioxane was treated with 11.8 g selenium dioxide at room temperature and the mixture was heated at 100 C. for 15 hours. After adding 2.5 g selenium dioxide, heating was continued one hour, the mixture cooled, filtered, and the cake washed with ethyl acetate. The filtrate and washings were evaporated to dryness in vacuo. The residual dark oil was taken up in methylene chloride, filtered and the solvent evaporated. The residue was crystallized from a small amount of methylene chloride to provide the title aldehyde. 1 H--NMR(CDCl3)ppm (delta): 7.87 (dd, 1H), 9.06 (d, 1H), 9.43 (d, 1H), 10.0 (s, 1H).Step A-Preparation of pyrimidine-4-yl formaldehyde Pyrimidine-4-yl formaldehyde was prepared from 4-methyl pyrimidine through a reference described in M. C. Liu et al., J Med Chem., 1995, 38 (21), 4234-4243.By the procedure of Example 2, using the following carboxaldehydes in place of 2-pyridinecarboxaldehyde: 4-pyrimidinecarboxaldehyde 2-pyrazinecarboxaldehyde 2-pyrrolecarboxaldehyde 2-thiazolecarboxaldehyde 4-thiazolecarboxaldehydeBy the procedure of Example 23, using in place of 2-pyridinecarboxaldehyde, the following carboxaldehydes: 2-pyrimidinecarboxaldehyde 2-pyrrolecarboxaldehyde 2-pyrazinecarboxaldehyde 4-pyrimidinecarboxaldehyde 2-thiazolecarboxaldehyde 4-thiazolecarboxaldehydeTo a solu tion of e thyl (S)-2-((S)-pyrrolidine-2- carboxamido)-9-(5, 6, 7, 8-tetrahydro-l, 8-naphthyridin-2-yl)nonanoate (50 mg, 0.08 mmol, 1 equiv) in 0.5 mL MeOH was added General procedure: To a stirred solution of 8, 9, or 20 (12.90 mmol) in i-PrOH (40 mL), aniline (15.48 mmol) anddiphenyl phosphite (20.64 mmol) were added. The mixture was stirred at room temperature for 4 h. The reaction mixture evaporated to dryness under reduced pressure. The residue was purified bysilica gel column chromatography (Petroleum ether/Ethyl acetate, 6:1) to give the titled compound 10a, 10b, or 21 as a white solid.

Molecular Weight:108.10
XLogP3:-0.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:108.032362755
Monoisotopic Mass:108.032362755
Topological Polar Surface Area:42.8
Heavy Atom Count:8
Complexity:84.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes