Cesium fluoride → 5'-Ethenyl-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618769노트

반응식

HRID 1618769 반응식
Br[C:2]1[N:7]=[C:6]2[C:8]3([CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH2:9][N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[C:5]2=[CH:4][C:3]=1[N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[F-].[Cs+].[CH2:42]([Sn](CCCC)(CCCC)C=C)[CH2:43]CC>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:42]([C:2]1[N:7]=[C:6]2[C:8]3([CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[CH2:9][N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[C:5]2=[CH:4][C:3]=1[N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)=[CH2:43]

참가 물질

6

반응물 3

HCID 25953Cesium fluorideHCID 81998TributylvinyltinHCID 866642805'-Bromo-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

생성물 1

HCID 672849095'-Ethenyl-1'-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

To a stirred solution of 5′-bromo-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (140 mg, 0.237 mmol) in 1,4-dioxane (4 mL) was added bis(tri-tert-butylphosphine)palladium (0) (12.12 mg, 0.024 mmol), cesium fluoride (36 mg, 0.237 mmol) and tri-n-butyl(vinyl)tin (90 μL, 0.285 mmol) and the reaction was heated at 120° C. for 3 h in the microwave. After this time the reaction was partitioned between EtOAc (50 mL) and water (15 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. The crude reaction was purified by column chromatography on silica gel (DCM to DCM:MeOH:—NH4OH (9:1:0.4), 1:0 to 2:1 as eluent) to give 5′-ethenyl-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 8.66-8.80 (1H, m), 7.85-7.96 (3H, m), 7.73 (1H, dd, J=9.3, 6.0 Hz), 7.42 (1H, ddd, J=6.8, 4.8, 2.1 Hz), 7.23-7.30 (1H, m), 7.09 (1H, dd, J=17.2, 10.8 Hz), 6.30 (1H, dd, J=17.3, 2.6 Hz), 5.96 (1H, s), 5.18-5.36 (1H, m), 4.23-4.32 (2H, m), 3.93-4.03 (2H, m), 3.77 (4H, t, J=4.6 Hz), 3.61-3.69 (2H, m), 2.68-2.80 (4H, m), 2.27-2.47 (5H, m), 1.77-1.90 (2H, m). Mass Spectrum (ESI) m/e=538.2 (M+1).

후처리

  1. customAfter this time the reaction was partitioned between EtOAc (50 mL) and water (15 mL)
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude reaction
  6. customwas purified by column chromatography on silica gel (DCM to DCM:MeOH:—NH4OH (9:1:0.4), 1:0 to 2:1 as eluent)

출처 및 근거

ORD 기록
ord-a377bc5fce4a4b99a543dfce84f70cf2
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

반응 노트

불러오는 중…