Synthetic Route of 63012-03-3, 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. 63012-03-3, name is (3-Chlorophenyl)(phenyl)methanol. A new synthetic method of this compound is introduced below.
To the mixture of (3-chlorophenyl)(phenyl)methanol (42.6 mg, 0.195 mmol), (cyanomethyl)trimethylphosphonium iodide (63.2 mg, 0.26 mmol) and 8-((2S,5R)-2,5- dimethylpiperazin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile, TFA (44.6 mg, 60 %wt, 0.065 mmol) in propanenitrile (0.3 mL) was added Hunig?s base (0.114 mL, 0.65 mmol). The reaction mixture was stirred at 110 C for 5 hours. The crude material was purified via preparative LC/MS with the following conditions: (1934) Column: XBridge C18, 200 mm x 19 mm, 5 mm particles; Mobile Phase A: 5:95 acetonitrile: water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: a 0 minute hold at 50 % B, 50-90 % B over 20 minutes, then a 4 minute hold at 100 % B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the product were combined and dried via centrifugal evaporation. The yield of diastereomeric product was 7.4 mg. Calculated molecular weight 498.03. Analytical LC/MS was used to determine the final purity. Injection 1 conditions: Column: Waters XBridge C18, 2.1 mm x 50 mm, 1.7 mm particles; Mobile Phase A: 5:95 (1935) acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 (1936) acetonitrile:water with 10 mM ammonium acetate; Temperature: 50 C; Gradient: 0 %B to 100 %B over 3 min, then a 0.50 min hold at 100 %B; Flow: 1 mL/min; Detection: MS and UV (220 nm). Injection 1 results: Purity: 99.4 %; Observed Mass: 498.12; Retention Time: 2.74 min. Injection 2 conditions: Column: Waters XBridge C18, 2.1 mm x 50 mm, 1.7 mm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1 % trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50 C; Gradient: 0 %B to 100 %B over 3 min, then a 0.50 min hold at 100 %B; Flow: 1 mL/min; Detection: MS and UV (220 nm). Injection 2 results: Purity: 98.1 %; Observed Mass: 498.13; Retention Time: 1.83 min
At the same time, in my other blogs, there are other synthetic methods of this type of compound,63012-03-3, (3-Chlorophenyl)(phenyl)methanol, and friends who are interested can also refer to it.
Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; VELAPARTHI, Upender; CHUPAK, Louis S.; DARNE, Chetan Padmakar; DING, Min; GENTLES, Robert G.; HUANG, Yazhong; KAMBLE, Manjunatha Narayana Rao; MARTIN, Scott W.; MANNOORI, Raju; MCDONALD, Ivar M.; OLSON, Richard E.; RAHAMAN, Hasibur; JALAGAM, Prasada Rao; ROY, Saumya; TONUKUNURU, Gopikishan; VELAIAH, Sivasudar; WARRIER, Jayakumar Sankara; ZHENG, Xiaofan; TOKARSKI, John S.; DASGUPTA, Bireshwar; REDDY, Kotha Rathnakar; RAJA, Thiruvenkadam; (0 pag.)WO2020/6018; (2020); A1;,
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