تفاعل #683244

ord-e8b865acecab4916b4cf06e0058c4bce

المذيبات

ظروف التفاعل

درجة الحرارة
125°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىThe mixture was purged with argon
  2. 2
    أخرىThe mixture was purged with argon
  3. 3
    أخرىsealed
  4. 4
    أخرىThe DME layer of the reaction mixture was collected
  5. 5
    أخرىthe solid precipitates
  6. 6
    أخرىwere triturated with methanol (2×10 mL)
  7. 7
    تركيزconcentrated
  8. 8
    أخرىThe solid residue was partitioned between EtOAc (20 mL) and aq. HCl (1 N, 20 mL)
  9. 9
    تركيزThe aqueous layer was concentrated under reduced pressure
  10. 10
    أخرىthe obtained light yellow solid was triturated with methanol (8 mL)
  11. 11
    أخرىThe supernant was isolated via filtration
  12. 12
    تركيزconcentrated

الإجراء التجريبي

To a microwave vial were charged with 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine (500 mg, 1.95 mmol), 4-borono-2-fluorobenzoic acid (1.07 g, 5.83 mmol), aqueous Na2CO3 (2 M, 4.86 mL) and DME (10 mL). The mixture was purged with argon, then followed by addition of Pd(PPh3)4 (225 mg, 0.194 mmol). The mixture was purged with argon, sealed and heated via microwave reactor at 125° C. for 20 min, and then at 130° C. for another 40 min. The DME layer of the reaction mixture was collected, and the solid precipitates were triturated with methanol (2×10 mL). Methanol supernatants were combined with DME layer, and concentrated. The obtained residue was stirred with Et2O (2×60 mL), and the Et2O supernatants were discarded. The solid residue was partitioned between EtOAc (20 mL) and aq. HCl (1 N, 20 mL). The EtOAc layer was stripped with 1N HCl (2×5 mL), and the aqueous layers were combined. The aqueous layer was concentrated under reduced pressure, and the obtained light yellow solid was triturated with methanol (8 mL). The supernant was isolated via filtration and concentrated. 4-(2-Amino-5-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-2-fluorobenzoic acid (0.844 g, 2.67 mmol, 137% yield) was obtained as light yellow foam. LCMS (m/z) 317.2 (MH+) 0.46 min.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09242996B2uspto-grants-2016_01