Reference of 45695-56-5, 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. 45695-56-5, name is Pyrimidine-2-carboximidamide. A new synthetic method of this compound is introduced below.
Compound 159 Enantiomers of racemic mixture 159: 159a and 159b A mixture of compound 129 (4 g crude), 2-pyrimidinecarboximidamide (2.35 g, 19.2 mmol) and 1 , 4-dioxane (25 mL) was stirred at 40C for 72 hours and allowed to reach room temperature. The reaction mixture was evaporated to dryness to afford a brown residue. This residue and phosphorus oxychloride (20.9 mL, 225 mmol) were stirred at 120C for 45 minutes in a round bottomed flask. The reaction mixture was concentrated in vacuo at 50C and co evaporated with toluene (2 x 100 mL). The residue was dissolved in dichloromethane (250 mL) and washed with saturated aqueous sodium bicarbonate (100 mL), dried (Na2S04) and evaporated to afford a dark brown residue. This residue was purified using silica gel column chromatography (dichloromethane in heptane from 50 to 100%) to methyl 6-chloro-4-(3,4- difluorophenyl)-4-methyl-2-(pyrimidin-2-yl)- 1 ,4-dihy dropyrimidine-5 -carboxylate (1800 mg) as light yellow solid. A solution of methyl 6-chloro-4-(3,4-difluorophenyl)- 4-methyl-2-(pyrimidin-2-yl)-l,4-dihy dropyrimidine-5 -carboxylate (900 mg) in 1 , 4- dioxane (10 mL) in a microwave-vial was stirred and purged with nitrogen for 10 minutes. Then tetramethyltin (494 mu, 3.56 mmol) was added followed by bis (tri-t- butylphosphine) palladium (0) (243 mg, 0.475 mmol) and the vial was flushed with nitrogen and capped. The reaction mixture was heated under microwave irradiation at 140C for 30 minutes and allowed to reach room temperature. The reaction mixture was stirred and purged with nitrogen for 10 minutes, bis(tri-t-butylphosphine) palladium (0) (121 mg, 0.238 mmol) was added and the vial was flushed with nitrogen and capped. The reaction mixture was heated by microwave irradiation at 145C for 30 minutes and allowed to reach room temperature. The reaction mixture was concentrated in vacuo. The obtained residue was mixed with dichloromethane (100 mL) and the orange precipitate was filtered off. The filtrate was washed with water (2 x 20 mL), dried (Na2S04) and concentrated in vacuo. The obtained residue was purified using silica gel column chromatography (ethyl acetate in heptane from 20 to 100%) to afford compound 159 as yellow sticky oil. Method A; Rt: 0.86 m/z; 359.2 (M+H)+ Exact mass: 358.1.Racemix mixture 159 was purified by Prep SFC (Stationary phase: Chiralpak Diacel AD 30 x 250 mm), Mobile phase: C02, Ethanol), yielding compound 159a and 159b as yellow powders. Columns: AD-H 250 mm x 4.6 mm; Flow: 3 ml/min; Mobile phase: 10 % EtOH (containing 0.2% iPrNH2) hold 15.00 min; Temperature: 30C; compound 159a: Rt (3.2 min), compound 159b Rt (4.5 min). 1H NMR (360 MHz, CHLOROFORM- , tautomeric mixture (-9/1), main isomer desribed) delta ppm 1.96 (s, 3 H), 2.34 (s, 3 H), 3.49 (s, 3 H), 7.04 (dt, J=10.0, 8.0 Hz, 1 H), 7.19 – 7.24 (m, 1 H), 7.30 (ddd, J=12.0, 8.0, 3.0 Hz, 1 H), 7.40 (t, J=5.0 Hz, 1 H), 8.41 (br. s., 1 H), 8.86 (d, J=5.0 Hz, 2 H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,45695-56-5, its application will become more common.
Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin Yvonne Paul; ROMBOUTS, Geert; VERSCHUEREN, Wim Gaston; RABOISSON, Pierre Jean-Marie Bernard; WO2013/102655; (2013); A1;,
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