ChemicalBook CAS DataBase List (R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine

(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine synthesis

6synthesis methods

Product Name:(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine
CAS Number:109838-85-9
Molecular formula:C9H16N2O2
Molecular Weight:184.24

420-37-1 Synthesis

420-37-1
235 suppliers
$17.00/5g

143673-66-9 Synthesis

143673-66-9
121 suppliers
$9.00/250mg

(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine

109838-85-9
182 suppliers
$40.00/500 mg

Yield:109838-85-9 71.5%

Reaction Conditions:

Stage #1:trimethoxonium tetrafluoroborate;(R)-3-(1-methylethyl)-piperazine-2,5-one in dichloromethane at 20; for 41 h;
Stage #2: with ammonia;water in dichloromethane at 0; for 1 h;

Steps:

1.A; 2.A (S)-Methyl 2-(5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxamido)-4-(dimethylamino)-2-methylbutanoate (9a)
Step A: Preparation of (R)-2-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (1): To a 2 L round-bottomed flask were added (R)-3-isopropylpiperazine-2,5-dione (20.7 g, 133 mmol), Me₃OBF₄ (49.0 g, 331 mmol) and CH₂Cl₂ (500 mL). The slurry was stirred vigorously at room temperature under nitrogen atmosphere. After stirring 18 hours, the slurry became a clear solution with very viscous yellow oil settling on the bottom of the flask. An additional equivalent of Me₃OBF₄ (19.6 g, 133 mmol) was added and the mixture was stirred at room temperature. After 23 hours, the mixture was cooled in an ice bath, and 200 g of ice and 100 mL of concentrated ammonium hydroxide solution (28%) were added to the reaction mixture. The reaction mixture was stirred in an ice bath for 1 hour. The layers were separated and aqueous layer was extracted with CH₂Cl₂ (2*50 mL). The combined organic layers were washed with saturated NaHCO₃ solution (2*100 mL) and brine (100 mL), dried over K₂CO₃, filtered through a Celite pad, and concentrated under reduced pressure to provide 25.9 g of light brown oil. The crude material was purified by chromatography with 1:4 ether/pentane to provide 17.464 g of compound 1 as a colorless oil (71.5% yield). ¹H NMR (400 MHz, CDCl₃) δ 4.08-3.94 (m, 3H), 2.95 (s, 3H), 2.87 (s, 3H), 2.30-2.18 (m, 1H), 1.04 (d, J=7.03 Hz, 3H), 0.76 (d, J=6.64 Hz, 3H).