تفاعل #79888

ord-d74a51b4a91e47d69911f3e711c6116b

ظروف التفاعل

درجة الحرارة
80°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىA precipitate formed after 20 minutes
  2. 2
    أخرىReaction
  3. 3
    درجة الحرارةto cool to room temperature
  4. 4
    أخرىthe organic solvent was removed under reduced pressure
  5. 5
    أخرىThe product was partitioned between the aqueous sodium carbonate layer and ethyl acetate
  6. 6
    استخلاصThe aqueous layer was further extracted with ethyl acetate three times
  7. 7
    غسيلwashed with water and brine
  8. 8
    تجفيفdried over magnesium sulfate
  9. 9
    تركيزpartially concentrated until a precipitate
  10. 10
    أخرىformed
  11. 11
    ترشيحThe solid was filtered
  12. 12
    غسيلwashed with ethyl acetate
  13. 13
    أخرىdried under a high vacuum

الإجراء التجريبي

A mixture of 4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (3.0 g, 7.15 mmol) in ethylene glycol dimethyl ether (100 mL) was treated with 4-(benzyloxy)phenylboronic acid (1.79 g, 7.87 mmol), tetrakis(triphenylphosphine)palladium (0.496 g, 0.429 mmol), and a solution of sodium carbonate (1.83 g, 17.16 mmol) in water (50 mL). A precipitate formed after 20 minutes. Reaction was stirred for 5 hours at 80° C. under a nitrogen atmosphere. The mixture was allowed to cool to room temperature and the organic solvent was removed under reduced pressure. The product was partitioned between the aqueous sodium carbonate layer and ethyl acetate. The aqueous layer was further extracted with ethyl acetate three times. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, and partially concentrated until a precipitate formed. The solid was filtered, washed with ethyl acetate, and dried under a high vacuum. Yielded 2.06 g (61%) of 5-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine. 1H NMR (DMSO-d6, 400 MHz) δ 8.64(s, 1H), 7.88(s, 1H), 7.52-7.33(m, 7H), 7.08-7.05(d, 2H, J=12 Hz), 5.15(s, 2H), 4.82-4.78 (m, 1H), 3.95-3.89(m, 4H), 2.21-2.13(m, 2H), 1.98-1.96(m, 2H), 1.85-1.75(m, 4H); Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 8.356 min.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06713474B2uspto-grants-2004_03