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Dimethyl Sulfoxide → 1-(7-fluoro-3-methyl-2-pyridin-2-ylquinolin-4-yl)-6-morpholin-4-ylspiro[2H-indole-3,4'-oxane]

HRID 1618491
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HRID 1618491 반응식
Br[C:2]1[CH:7]=[C:6]2[N:8]([C:16]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]=[C:18]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[C:17]=3[CH3:33])[CH2:9][C:10]3([CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.CS(C)=O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.O.[Cu]I>[F:26][C:22]1[CH:21]=[C:20]2[C:25]([C:16]([N:8]3[C:6]4[C:5](=[CH:4][CH:3]=[C:2]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH:7]=4)[C:10]4([CH2:11][CH2:12][O:13][CH2:14][CH2:15]4)[CH2:9]3)=[C:17]([CH3:33])[C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[N:19]2)=[CH:24][CH:23]=1
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참가 물질

8

반응물 4

HCID 679Dimethyl SulfoxideHCID 8083MorpholineHCID 11430Potassium CarbonateHCID 672857806-Bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]

생성물 1

HCID 672845151-(7-fluoro-3-methyl-2-pyridin-2-ylquinolin-4-yl)-6-morpholin-4-ylspiro[2H-indole-3,4'-oxane]

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매
HCID 962Water용매
HCID 6344Dichloromethane용매

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온도
120 °C

실험 절차

A suspension of 6-bromo-1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (100 mg, 0.198 mmol), morpholine and DMSO (2.5 mL) was degassed with argon for 15 min in a Schlenck tube. To the mixture was added copper (I) iodide (8 mg, 40 μmol), 1-(−)-proline (9 mg, 79 mmol) and potassium carbonate (82 mg, 595 μmol) and the mixture was heated at 120° C. overnight. After this time the reaction was cooled to rt and diluted with DCM (100 mL) and water (40 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (hexane:EtOAc, 1:0 to 0:1) gave the desired product as a yellow oil. The product was further purified by reverse phase HPLC to give 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]. 1H NMR (400 MHz, chloroform-d) δ ppm 8.76 (1H, dd, J=3.7, 1.0 Hz), 7.75-8.00 (4H, m), 7.41 (1H, ddd, J=7.1, 5.0, 1.6 Hz), 7.21-7.27 (1H, m), 7.13 (1H, d, J=8.2 Hz), 6.35 (1H, dd, J=8.2, 2.3 Hz), 5.61 (1H, d, J=2.3 Hz), 3.96-4.09 (3H, m), 3.89-3.96 (1H, m), 3.70-3.79 (4H, m), 3.49-3.60 (2H, m, J=12.2, 12.2, 2.9, 2.7 Hz), 2.91-3.04 (4H, m), 2.38 (3H, s), 2.09-2.22 (2H, m), 1.76-1.93 (2H, m). Mass Spectrum (ESI) m/e=511 (M+1).

후처리

  1. customwas degassed with argon for 15 min in a Schlenck tube
  2. temperatureAfter this time the reaction was cooled to rt
  3. dry with materialThe separated organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-a11ca004de114b71b49cfe29c4a075ca
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08765940B2

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