4-chloro-5,8-dihydro-6H-pyrido[3,4-d]pyriMidine-7-carboxylic acid tert-butyl ester

tert-Butyl 4-chloro-5, 6-dihydropyrido[3, 4-d]pyrimidine-7(8H)-carboxylate STEP C: A mixture of 4-hydroxy-5, 8-dihydro-6H-pyrido[3, 4-d]pyrimidine-7- carboxylic acid ter/-butyl ester ( 1 .4 g, 5.6 mmol) and triphenylphosphine (2.9 g, 1 1.1 mmol) was stirred in DCE (41 mL) until the solution became clear, and then carbon tetrachloride ( 1.6 mL, 16.7 mmol) was added. The reaction mixture was heated to 70°C and stirred for 2.5 hours. The volatiles were removed in vacuo and the crude material was directly purified by flash chromatography on silica gel (0-50percent EtOAc/ heptanes) to afford the title compound as an off-white solid (1.31 g, 87percent yield). MS (ESI) m/e (M+HThe Preparation of Compound 12: Compound 12F (1.6 g, 6.3 mmol), triphenylphosphine (3.33 g, 12.6 mmol) and tetrachloromethane (2.93 g, 18.9 mmol) were mixed in 1, 2-dichloroethane (1, 2-DCE, 64 mL), heated to 70° C. for 1 hour. The reaction was monitored via TLC (DCM/Methanol=10:1). The reaction mixture was concentrated and purified by silica gel chromatography to obtain a purified compound 12 (1.38 g, yield: 81percent) as a light yellow solid.tert- Butyl 4-chloro-5, 8-dihydropyrido[3, 4-d]pyrimidine-7(6H)-carboxylate (700 mg, 2.60 mmol) was dissolved in tetrahydrofuran (7 mL). Sodium ethoxide (25% w/w, 1.12 mL, 3.9 mmol) was added and stirring was continued for 15 min. The reaction was quenched with aqueous ammonium chloride (3.5 mL) and water (20 mL) and extracted with ethyl acetate (3 × 20 mL). The combined organics were dried (MgSO4), concentrated and the residue was purified by flash chromatography (elution with 0-60% ethyl acetate in heptane) to afford the title compound (729 mg, 100%) as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 8.58 (s, 1H), 5.32 (s, 1H), 4.56 (s, 2H), 4.47 (q, J = 7.05 Hz, 2H), 3.69 (t, J = 5.81 Hz, 2H), 2.70 (t, J = 5.38 Hz, 2H), 1.51 (s, 9H), 1.42 (s, 3H). [M+H] = 280.0.A mixture of tert-Butyl 4-chloro-5, 6-dihydropyrido[3, 4-d]pyrimidine-7(8H)-carboxylate (226 mg, 0.84 mmol) in DMA (2.5 mL) was treated with (3R)-3-fluoropyrrolidine (1.58 g, 1.26 mmol) and DIEA (0.44 mL, 2.51 mmol) and the mixture was heated at 80oC for 16 h. The mixture was cooled, concentrated under vacuum and the residue was purified by flash LC (elution with 0-75% A in B, where A is 10% methanol in ethyl acetate and B is heptane) to afford the title compound (212 mg, 78%) as a colorless semi-solid. [M+H] = 323.1.A mixture of A mixture of

Molecular Weight:269.73
XLogP3:1.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:269.0931045
Monoisotopic Mass:269.0931045
Topological Polar Surface Area:55.3
Heavy Atom Count:18
Complexity:319
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes