6-CYANONICOTINICACID

To a solution of the nicotinic acid N-oxide (51 g, 0.37 mol) in 1.2 L [OF DMF, NACN] (54 g, 1.1 mol) was added, followed by triethylamine (255 mL, 1.83 mol) and TMSCI (185 mL). The reaction mixture was stirred at [110°C] for 10 h, filtered and the filtrate was concentrated. The residue was dissolved in 100 mL of 2N HCI and extracted with methylene chloride. The organic layers were combined, concentrated and recrystallised from water to yield 12 g (22percent) of the product.6-Cyanonicotinic acid (9.547 g, 64.45 mmol) was suspended in thionyl chloride (40 mL, 548 mmol). The flask was equipped with a reflux condenser and a drying tube. The reaction mixture was heated at reflux for 17 hours. The excess thionyl chloride was removed in vacuo. The residue was taken up in toluene and concentrated to yield the corresponding acid chloride (10.879 g) as an orange-brown solid.A. 6-Cyanonicotinic acid (9.547 g, 64.45 mmol) was suspended in thionyl chloride (40 mL, 548 mmol). The flask was equipped with a reflux condenser and a drying tube. The reaction mixture was heated at reflux for 17 hours. The excess thionyl chloride was removed in vacuo. The residue was taken up in toluene and concentrated to yield the corresponding acid chloride (10.879 g) as an orange-brown solid. B. The product prepared in step A (10.87 g, 65.3 mmol) was suspended in 60 mL toluene in a 3-neck flask. Methyl-N-methyl-2-pyrroleacetate (8.0 mL, 55.6 mmol) was added to the reaction. The flask was equipped with a reflux condenser and an argon bubbler. Argon was gently bubbled through the reaction as it was heated at 105 C. for 16 hours. The reaction was then diluted with 400 mL chloroform and washed four times with 200 mL 10% Na2CO3 solution. The organics were dried with MgSO4 and treated with charcoal then filtered and concentrated. The residue was triturated with 70 mL methanol, filtered, and rinsed twice more with 25 mL methanol. The solid was then dried under vacuum to yield the acylated pyrrolyl acetate (12.126 g, 42.8 mmol) as a tan-brown powder.Preparation 466- Cvano-nicotinoyl chloride6-Cyano-nicotinic acid (120mg, 810mueta?omicronIota) was suspended in toluene (1 ml_) and thionyl chloride (1 19muIota_, 1 .62mmol) was added dropwise followed by one drop of DMF. The reaction mixture was refluxed for 2.5 hours and then allowed to cool to room temperature for 18 hours. The solvents were removed in vacuo and the residue was azeotroped with toluene to furnish the title compound as a brown oil (134mg) which was used in further experiments without purification. LCMS: m/z 167.02 M+H+.6-cyano-N-((3R)-1-((3-(cyclopropylmethyl)-1-isopropyl-2, 4-dioxo-1, 2, 3, 4-tetrahydroquinazolin-6-yl)carbamoyl)piperidin-3-yl)nicotinamide T3P (442 muL, 0.75 mmol) was added to a solution of (R)-3-amino-N-(3-(cyclopropylmethyl)-1-isopropyl-2, 4-dioxo-1, 2, 3, 4-tetrahydroquinazolin-6-yl)piperidine-1-carboxamide (100 mg, 0.25 mmol),

Molecular Weight:148.12
XLogP3:0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:148.027277375
Monoisotopic Mass:148.027277375
Topological Polar Surface Area:74
Heavy Atom Count:11
Complexity:206
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes