Category: 1250967-81-7

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1250967-81-7, name is 2-Chloro-4-isopropoxypyrimidine. A new synthetic method of this compound is introduced below., name: 2-Chloro-4-isopropoxypyrimidine

A mixture of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (5 mg, 8 pmol), 18F (15 mg, 0.04 mmol) ,2-chloro-4-isopropoxypyrimidine (8 mg, 0.05 mmol), BINAP (5 mg, 8 pmol), Pd2(dba)3 (2 mg, 4 pmol) and Cs2C03 (20 mg, 0.06 mmol) in toluene (1 mL) was heated in a sealed tube to 110 C overnight, then was cooled to RT and concentrated in vacuo. The residue was dissolved in THF (0.5 mL), MeOH (0.5 mL), and H20 (0.5 mL). LiOH.H20 (17 mg, 0.4 mmol) was added and the reaction was stirred at RT for 14 h, then was concentrated in vacuo. The residue was taken up in EtOAc (2 mL)/H20 (1 mL), and the solution was adjusted to pH ~ 5 with IN aq. HC1. The mixture was extracted with EtOAc (3 x 2 mL); the combined organic extracts were dried (MgS04) and concentrated in vacuo. The residue was dissolved in DMF and purified via preparative LC/MS: Column: XBridge Cl 8, 200 mm x 19 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: a 0-min hold at 18% B, 18-58% B over 20 min, then a 4-min hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound (bis-TFA salt, 1 mg, 3% yield; 84% purity by LC-MS). LCMS, [M + H]+ = 468.4. NMR (500 MHz, DMSO-de) d 8.31 (s, 1H), 8.08 (d, J= 5.7 Hz, 1H), 7.92 (s, 1H), 6.18 (d, J= 5.7 Hz, 1H), 5.10 – 4.98 (m, 1H), 4.75 (s, 1H), 3.72 (s, 3H), 2.68 – 2.59 (m, 1H), 2.27 (s, 3H), 2.01 – 1.47 (m, 8H), 1.21 – 1.15 (m, 6H). hLPAi IC50 = 1014 nM.

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Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; SHI, Yan; WANG, Ying; CHENG, Peter Tai Wah; LI, Jun; WALKER, Steven J.; (147 pag.)WO2019/126089; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 1250967-81-7, 2-Chloro-4-isopropoxypyrimidine, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, 1250967-81-7, blongs to pyrimidines compound. HPLC of Formula: C7H9ClN2O

To a RT solution of Intermediate 2 (5 mg, 0.01 mmol) in n-BuOH (0.7 mL) were added 2-chloro-4-isopropoxypyrimidine (4 mg, 0.02 mmol) and iPr2NEt (9 pL, 0.05 mmol). The reaction was stirred at 180 C for 80 min, then was cooled to RT. THF (0.8 mL)/MeOH (0.4 mL)/H20 (0.4 mL) were added to the reaction mixture, followed by LiOH.H20 (3 mg, 0.07 mmol) at RT. The reaction was stirred at RT overnight, then was concentrated in vacuo and the residue was diluted with H20 (5 mL). The pH of the mixture was adjusted with aq. IN HC1 to ~5 and it was extracted with EtOAc (3 x 5 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: Waters XBridge C18, 19 x 200 mm, 5-mha particles; Guard Column: Waters XBridge C18, 19 x 10 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 20 min, then a 4-min hold at 100% B; Flow rate: 20 mL/min. Fractions containing the desired product were combined and concentrated via centrifugal evaporation to provide the title compound (6.5 mg, 8.7 pmol, 67 % yield). LCMS, [M+H]+ = 482.3. NMR (500 MHz, DMSO-de) d 8.42 (s, 1H), 8.06 (br s, 1H), 7.93 (s, 1H), 6.23 (br d, J=6.l Hz, 1H), 5.26 – 5.16 (m, 1H), 5.06 (br s, 2H), 4.84 – 4.77 (m, 1H), 3.92 (s, 3H), 2.68 – 2.60 (m, 1H), 2.42 (s, 3H), 2.06 – 1.44 (m, 8H), 1.22 (d, J=6.l Hz, 6H). hLPAi IC50 = 29 nM.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1250967-81-7, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; SHI, Yan; WANG, Ying; CHENG, Peter Tai Wah; LI, Jun; WALKER, Steven J.; (147 pag.)WO2019/126089; (2019); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia