반응 #75962

ord-18628cf1a5f145ae89ab206458059a7c

반응 조건

온도
85°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도The reaction was cooled
  2. 2
    여과filtered through a pad of Celite® with the aid of ethyl acetate
  3. 3
    농축The filtrate was concentrated in vacuo
  4. 4
    기타to remove excess solvents
  5. 5
    기타the resulting oil was purified by flash chromatography on silica gel
  6. 6
    세척eluted on a gradient from 75:25 to 25:75 hexanes/ethyl acetate

실험 절차

Argon was bubbled through a mixture of (2S)-N-{[(2R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-N-(phenylmethyl)-3-(phenyloxy)-1-propanamine (Example 88, 100 mg, 0.16 mmol) and 4-chloro-2-pyridinecarboxamide in toluene (1 mL), ethanol (1 mL), and 2M aqueous sodium carbonate (1 mL) for 10 minutes. Triphenylphosphine (4 mg, 0.016 mmol, 0.1 eq.) and palladium (II) acetate (1.0 mg, 0.004 mmol, 0.025 eq.) were added, and the mixture was stirred vigorously under argon at 85° C. overnight. The reaction was cooled and filtered through a pad of Celite® with the aid of ethyl acetate. The filtrate was concentrated in vacuo to remove excess solvents, and the resulting oil was purified by flash chromatography on silica gel eluted on a gradient from 75:25 to 25:75 hexanes/ethyl acetate. The title compound was obtained as a pale yellow oil (45 mg, 44%): 1H NMR (300 MHz, acetone-d6) δ8.57 (d, 1 H), 8.31 (d, 1 H), 7.96 (broad s, 1 H), 7.76 (dd, 1 H), 7.56-7.53 (m, 2 H), 7.45-7.41 (m, 2 H), 7.34-7.21 (m, 5 H), 6.91-6.86 (m, 4H), 6.80 (broad s, 1 H), 4.35-4.30 (m, 1 H), 4.26-4.18 (m, 2 H), 3.93-3.77 (m, 3 H), 2.98-2.87 (m, 4 H), 2.15-2.08 (m, 1 H), 1.73-1.59 (m, 1 H), 1,30-1.25 (m, 1 H), 0.88 (s, 9 H), 0.12 (s, 3 H), 0.08 (s, 3 H); MS m/z 638.4 (MH+).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06699860B2uspto-grants-2004_03