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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
Notes
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Reaction equation

HRID 1618491 reaction equation
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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 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]

Product 1

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

Reagents, catalysts & solvents

3
HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a11ca004de114b71b49cfe29c4a075ca
Source dataset
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08765940B2

Reaction notes

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