Electric Literature of 51674-77-2 ,Some common heterocyclic compound, 51674-77-2, molecular formula is C7H4ClN3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
(S)-(-)-tert-Butyl 3-aminopyrrolidine-l-carboxylate (500 mg, 2.68 mmol), DCM(30 mL), DIPEA (2 mL) and cyclopropanecarbonyl chloride (0.28 mL, 3.0 mmol) were combined at r.t. and stirred for 2 days. The reaction was diluted with DCM (100 mL), washed with water, dried (MgS04) and evaporated in vacuo to give a brown oil (866 mg). The crude product was combined with MeOH (10 mL) and 2M HCl in Et20 (5 mL) and stirred at r.t. for 3 days. The reaction mixture was then evaporated in vacuo to give a brown gum (746 mg). The crude compound, Intermediate 9 (500 mg, 1.48 mmol), n- butanol (16 mL) and DIPEA (2 mL) were combined in a sealed tube and heated to 130C for 15 days. The reaction mixture was evaporated onto silica and purified by flash chromatography on silica, eluting with 0-100% EtOAc in isohexane, to give a tan solid (779 mg). The product was combined with MeOH (10 mL) and 2N HCl in Et20 (7 mL) and stirred at r.t for 19 h. The reaction mixture was then evaporated in vacuo to give a brown glass (689 mg). The resulting amine intermediate (HCl salt, 50 mg) was combined with 4-chloropyrido[3,2-d]pyrimidine (50 mg) in «-butanol (5 mL) and DIPEA (1 mL). The reaction mixture was heated in a sealed tube under microwave irradiation to 160C for 2 h. The mixture was evaporated to dryness and purified by preparative HPLC to give the title compound (32 mg) as a brown glass. deltaEta (DMSO-d6) 8.94-8.90 (2H, m), 8.52 (1H, s), 8.42 (1H, d, J6.4 Hz), 8.28-8.22 (1H, m), 8.17 (1H, dd, J 8.5, 1.6 Hz), 7.91 (1H, dd, J 8.5, 4.2 Hz), 7.56 (1H, dd, J 8.8, 6.4 Hz), 7.08 (1H, t, J 9.1 Hz), 6.00 (1H, t, J 7.2 Hz), 4.47-4.39 (1H, m), 4.02 (1H, dd, J 10.4, 6.8 Hz), 3.97-3.86 (2H, m), 3.70 (1H, dd, J 10.4, 6.9 Hz), 2.50 (3H, d, J2.2 Hz), 2.32-2.22 (1H, m), 2.00-1.91 (1H, m), 1.65-1.55 (4H, m), 0.75-0.66 (4H, m). LCMS (ES+) 486 (M+H)+, RT 8.15 minutes (Method 3).
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 51674-77-2, 4-Chloropyrido[3,2-d]pyrimidine, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; UCB PHARMA S.A.; ALLEN, Daniel, Rees; BUeRLI, Roland; HAUGHAN, Alan, Findlay; MATTEUCCI, Mizio; OWENS, Andrew, Pate; RAPHY, Gilles; SHARPE, Andrew; WO2011/58108; (2011); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia