Reacción #683025

Ecuación de reacción

5-bromopyrazin-2-amine

2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

KOt-Bu

1,4-dioxane

→

5-cyclopropylpyrazin-2-amine

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe mixture was purged with Argon
2. 2
   Otropurge
3. 3
   Otrothe mixture was sealed
4. 4
   workup.ADDITIONTo the reaction mixture was added 2nd portion of PalladiumTetrakis (266 mg)
5. 5
   Temperaturathe reaction was heated at 160° C. via microwave reactor for 20 min
6. 6
   FiltraciónThe reaction mixture was filtered through a thin layer of Celite
7. 7
   Concentraciónthe filtrate was concentrated
8. 8
   OtroThe residue was triturated with EtOAc (6 mL)
9. 9
   Otrothe precipitates were removed via centrifugation and filtration
10. 10
    ExtracciónThe EtOAc supernatant was back extracted with aqueous TFA solution (3×3 mL, TFA/water—1 mL/10 mL)
11. 11
    workup.ADDITIONdiluted with acetonitrile (10 mL)
12. 12
    Temperaturafrozen

Procedimiento

To a microwave vial was charged with 5-bromopyrazin-2-amine (400 mg. 2.3 mmol), 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.16 g, 6.9 mmol), KOt-Bu (1M in t-BuOH, 9.2 mL), 1,4-dioxane (10 mL), and water (0.10 mL), and the mixture was purged with Argon, followed by addition of Palladium tetrakis (266 mg, 0.23 mmol) and final Argon purge, then the mixture was sealed and heated at 150° C. via microwave reactor for 20 min. To the reaction mixture was added 2nd portion of PalladiumTetrakis (266 mg) and the reaction was heated at 160° C. via microwave reactor for 20 min. The reaction mixture was filtered through a thin layer of Celite, and the filtrate was concentrated. The residue was triturated with EtOAc (6 mL), and the precipitates were removed via centrifugation and filtration. The EtOAc supernatant was back extracted with aqueous TFA solution (3×3 mL, TFA/water—1 mL/10 mL). The TFA solutions were combined, diluted with acetonitrile (10 mL), frozen and lyophilized to afford 5-cyclopropylpyrazin-2-amine in a yellow powder. The product after lyophilization was transferred to a vial, basified to pH>12 with sat. Na2CO3 (3 mL), extracted with EtOAc(4×6 mL), and the EtOAc extracts were combined, and concentrated and further dried under high vacuum, and final 5-cyclopropylpyrazin-2-amine free base was obtained (79 mg, 25.4% yield). LCMS (m/z): 136.1 (MH+), 0.30 min. 1H NMR (CD3OD) δ ppm 8.29 (d, J=1.2 Hz, 1H), 7.70 (d, J=1.6 Hz, 1H), 2.00-2.08 (m, 1H), 0.94-1.00 (m, 2H), 0.87-0.93 (m, 2H).

Fuente