Related Products of 1250967-81-7, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.1250967-81-7, name is 2-Chloro-4-isopropoxypyrimidine, molecular formula is C7H9ClN2O, molecular weight is 172.61, as common compound, the synthetic route is as follows.
To a 0C solution of Intermediate 1E (10 mg, 0.026 mmol) and 2-chloro-4- isopropoxy- pyrimidine (7 mg, 0.04 mmol) in DMF (0.3 mL) was added NaH (2 mg of a 60% dispersion in mineral oil, 0.05 mmol). The reaction mixture was stirred at RT for 1 h. LCMS indicated the formation of the two products. Water (0.4 mL) and MeOH (0.4 mL) were added to the reaction mixture, which was stirred for another 1 h at RT, then was concentrated in vacuo. The residue was diluted with H20 (1 mL) and the pH was adjusted with 1N aq. HC1 to ~5, then was extracted with EtOAc (3 x 2 mL). The combined organic extracts were washed with brine (2 mL), dried (MgS04) and concentrated in vacuo. The crude product was purified by preparative LC/MS (Column: XBridge Cl 8, 19 x 200 mm, 5-pm particles; Mobile Phase A: 5:95 MeCN:H20 with 0.1% TFA; Mobile Phase B: 95:5 MeCN:H20 with 0.1% TFA; Gradient: 15-55% B over 27 min, then a 3-min hold at 100% B; Flow: 20 mL/min). Fractions containing the desired product were combined and dried via centrifugal evaporation. The first eluting isomer was further purified by preparative LC/MS (Column: XBridge Shield RP18, 19 x 200 mm, 5-pm particles; Mobile Phase A: 5:95 MeCN:H20 with l0-mM aq. NH4OAc; Mobile Phase B: 95:5 MeCN:H20 with lO-mM aq. NH4OAc; Gradient: 21-46% B over 25 min, then a 2-min hold at 46% B; Flow: 20 mL/min) to give Example 249 (1.8 mg, 15% yield). Its estimated purity by LCMS analysis was 100%. LCMS, [M + H]+ = 483.4. NMR (500 MHz, DMSO-^e) d 8.28 (d, = 5.6 Hz, 1H), 7.84 (s, 1H), 7.51 (s, 1H), 6.53 (d, J= 5.6 Hz, 1H), 6.02 (s, 2H), 5.09 (p, J= 6.2 Hz, 1H), 4.72 (s, 1H), 4.11 (s, 3H), 2.26 (s, 3H), 1.96 – 1.41 (m, 8H), 1.25 (d, J= 6.2 Hz, 6H; the proton a to the carboxylic acid is not observed due to water suppression). hLPAi IC50 = 67 nM. The second eluting isomer was further purified by preparative LC/MS (Column: XBridge C18, 19 x 200 mm, 5-pm particles; Mobile Phase A: 5:95 MeCN:H20 with 10- mM aq. NH4OAc; Mobile Phase B: 95:5 MeCN:H20 with l0-mM aq. NH4OAc; Gradient: 10-50% B over 27 min, then a 5-min hold at 100% B; Flow: 20 mL/min) to give Example 250 (1.1 mg, 9% yield; 100% purity by LC/MS). LCMS [M + H]+ = 483.1. NMR (500 MHz, DMSO-i/e) d 8.28 (d, J= 5.7 Hz, 1H), 7.86 (d, J= 8.5 Hz, 1H), 7.51 (d, j= 8.7 Hz, 1H), 6.50 (d, j= 5.7 Hz, 1H), 6.00 (s, 2H), 5.18 – 5.07 (m, 1H), 4.72 (s, 1H), 4.11 (s, 3H), 2.26 (s, 3H), 1.91 – 1.43 (m, 8H), 1.18 (d, j= 6.2 Hz, 6H; the proton a to the carboxylic acid is not observed due to water-suppression). hLPAi IC50 = 41 nM.
Statistics shows that 1250967-81-7 is playing an increasingly important role. we look forward to future research findings about 2-Chloro-4-isopropoxypyrimidine.
Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; SHI, Yan; WANG, Ying; CHENG, Peter Tai Wah; SHI, Jun; TAO, Shiwei; CORTE, James R.; FANG, Tianan; LI, Jun; KENNEDY, Lawrence J.; KALTENBACH, III, Robert F.; JUSUF, Sutjano; (316 pag.)WO2019/126093; (2019); A1;,
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