Category: 78342-42-4

Reference of 78342-42-4, A common heterocyclic compound, 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, molecular formula is C9H16N2O2, 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.

To a solution of 3.32 g (18 mmol) of commercially available (2S)-2, 5- dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at-70 ¡ãC was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4- trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5percent ethyl acetate in hexanes) afforded 5.5 g of the title compound. [1H NMR] (500 MHz, [CDCL3)] [8] 7.33- 7.25 (m, 3H), 4.35-4. 31 (m, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.60 (t, [1H,] J = 3.4 Hz), 3.33 (dd, 1H, J = 4.6, 13.5 Hz), 3.03 (dd, [1H,] J = 7,13. 5 Hz), 2.25-2. 15 (m, [1H),] 1.0 (d, 3H, J = 7 Hz), 0.66 (d, 3H, J = 7 Hz).

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2004/7468; (2004); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 78342-42-4, A common heterocyclic compound, 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, molecular formula is C9H16N2O2, 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.

Example 1 Production of (2R,5S)-2-(2-(diethoxy-phosphoryl)ethyl)-2,5-dihydro-3,6-dimethoxy-5-isopropyl pyrazine 0.52 mol of (S)-2,5-dihydro-3,6-dimethoxy-2-isopropyl pyrazine are solved in 400 ml of absolute THF under argon and are cooled to -78¡ã C. Under stirring, 200 ml of a 2.7 M solution of butyl lithium (in heptane) (0.54 mol) are added in drops and slowly. Subse-quently, a solution of 0.52 mol of diethyl-(2-bromoethyl) phosphonate in 300 ml of absolute THF is added in drops and slowly during stirring, and the mixture is stirred for further 3 h at -78¡ã C. Then, 11.7 ml (about 0.2 mol) anhydrous acetic acid are added slowly. The reaction mixture is allowed to warm up slowly to room temperature. The solvent is removed, and the residue is solved in 600 ml of diethyl ether and washed with 200 ml of water. The aqueous phase is still extracted three times with each 100 ml of diethyl ether. The combined ether phases are dried over MgSO4, filtered and the solvent is removed in vacuo. The residue is solved in a mixture of diethyl ether and hexane (1:10) and filtered over a bed of silica gel. Thereby, first it is eluted with diethyl ether and hexane (1:5). Yield: about 70percent of a yellow liquid. 1H-NMR (CDCl3): 0.71, 1.04 (d, 6H, CH(CH3)2), 1.33 (t, 6H, P(O)(OCH2CH3)2), 1.68-2.25 (m, 4H, CHCH2CH2P), 3.65, 3.67 (s, 6H, OCH3), 4.02 (m, 1H), 4.10-4.20 (m, 4H, P(O)(OCH2CH3)2).

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Lindhorst, Thomas; Werner, Birgit; Bock, Holger; US2010/22478; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 78342-42-4, These common heterocyclic compound, 78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, 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.

An oven-dried microwave vial (2.0 – 5.0 mL volume) was charged with (2S)-2- isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (100 uL, 0.56 mmol). The reaction vial was flushed with argon, sealed with a cap and then further flushed with argon. Dry THF (2 mL) was added. The reaction vessel was cooled to -78 ¡ãC and n-BuLi (1.59M in hexanes; 0.74 mL, 1.18 mmol) was added dropwise. The reaction mixture was stirred at -78 ¡ãC for 30 min. 2- Bromoethanol (40 uL, 0.56 mmol) was added dropwise and the reaction mixture was allowed to warm to rt and stirred for 4h. The reaction mixture was cooled to 0 ¡ãC and a solution of 4- methylbenzenesulfonyl chloride (106 mg, 0.56 mmol) in THF (1 mL) was added. The reaction mixture was allowed to warm to rt and stirred for 2h. The reaction mixture was quenched with saturated aq. NH4CI (5 mL) and the aqueous mixture was extracted with DCM (3 x 10 mL). The organic extracts were combined, dried (Na2S04) and concentrated in vacuo. Purification by flash chromatography (25 g KP-SIL; 0percent to 40percent EtOAc in cyclohexane) afforded 2- [(2f?,5S)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl]ethyl 4-methylbenzenesulfonate (cf.r. >20: 1 , 107 mg) as a viscous yellow oil. LCMS (Method T2) Rt 1.60 min; m/z 383.1639 [M+H]+

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; BELLENIE, Benjamin Richard; CARTER, Michael Keith; CHEUNG, Kwai Ming Jack; DAVIS, Owen Alexander; HOELDER, Swen; LLOYD, Matthew Garth; VARELA RODRIGUEZ, Ana; (381 pag.)WO2018/215801; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem