Cesium carbonate → N-(7-cyclohexyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 468780노트

반응식

HRID 468780 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][N:8]=[C:7]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:6]=2.[CH:18]1([C:21]([NH2:23])=[O:22])[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C>[CH:12]1([C:7]2[CH:6]=[C:5]3[C:10]([CH:11]=[C:2]([NH:23][C:21]([CH:18]4[CH2:20][CH2:19]4)=[O:22])[N:3]=[CH:4]3)=[CH:9][N:8]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 80376CyclopropanecarboxamideHCID 866749423-Chloro-7-cyclohexyl-2,6-naphthyridine

생성물 1

HCID 67974796N-(7-cyclohexyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide수율 66%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

A mixture of 3-chloro-7-cyclohexyl-2,6-naphthyridine (80.0 mg, 0.324 mmol), cyclopropanecarboxamide (47.7 mg, 0.560 mmol), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (6.0 mg, 0.011 mmol), chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2-4′-6′-tri-1-pr-1,1′-biphenyl)][2-(2-aminoethyl)Ph]Pd(II) (9.2 mg, 0.012 mmol), and cesium carbonate (240.1 mg, 0.7369 mmol) in 1,4-dioxane (2 mL, 20 mmol) was heated at 90° C. for 2 hours. The reaction mixture was cooled to room temperature, diluted in ethyl acetate, washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 63.2 mg (66%) of N-(7-cyclohexyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.090, M+H=296.1, method=E; 1H NMR (400 MHz, DMSO) δ 11.02 (s, 1H), 9.28 (s, 1H), 9.19 (s, 1H), 8.55 (s, 1H), 7.72 (s, 1H), 2.89-2.73 (m, 1H), 2.14-2.03 (m, 1H), 1.96 (d, J=11.6 Hz, 2H), 1.84 (d, J=12.8 Hz, 2H), 1.74 (d, J=12.6 Hz, 1H), 1.63-1.51 (m, 2H), 1.43 (dd, J=25.4, 12.6 Hz, 2H), 1.34-1.18 (m, 1H), 0.85 (dd, J=8.3, 6.5 Hz, 4H).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via reverse phase HPLC

출처 및 근거

ORD 기록
ord-70f4266c3d4940d383ebd26258f732a8
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

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