Sodium t-butoxide → 1-(7-Fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

HRID 1618555Notes

Reaction equation

HRID 1618555 reaction equation
C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].[O:41]1[CH2:46][CH2:45][N:44]([C:47]2[CH:52]=[C:51]3[NH:53][CH2:54][C:55]4([CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[C:50]3=[CH:49][CH:48]=2)[CH2:43][CH2:42]1.Cl[C:62]1[C:71]2[C:66](=[CH:67][C:68]([F:72])=[CH:69][CH:70]=2)[N:65]=[C:64]([C:73]2[CH:78]=[CH:77][CH:76]=[C:75]([S:79]([CH3:82])(=[O:81])=[O:80])[CH:74]=2)[C:63]=1[CH3:83]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:72][C:68]1[CH:67]=[C:66]2[C:71]([C:62]([N:53]3[C:51]4[C:50](=[CH:49][CH:48]=[C:47]([N:44]5[CH2:43][CH2:42][O:41][CH2:46][CH2:45]5)[CH:52]=4)[C:55]4([CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[CH2:54]3)=[C:63]([CH3:83])[C:64]([C:73]3[CH:78]=[CH:77][CH:76]=[C:75]([S:79]([CH3:82])(=[O:80])=[O:81])[CH:74]=3)=[N:65]2)=[CH:70][CH:69]=1

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]HCID 672853434-Chloro-7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)quinolineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 509387191-(7-Fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (24.5 mg, 0.051 mmol), Pd2dba3 (23.6 mg, 0.026 mmol), sodium tert-butoxide (49.5 mg, 0.52 mmol), 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (47.1 mg, 0.17 mmol) (described herein), and 4-chloro-7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)quinoline (60 mg, 0.17 mmol) (described herein) in toluene (1.7 mL) was stirred at 100° C. for 60 min, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine, then the organic layer dried (MgSO4) and concentrated. Column chromatography afforded 1-(7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran] as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.24 (1H, d, J=2.0 Hz), 8.07 (1H, d), 7.96 (1H, d), 7.76 (3H, m), 7.31 (1H, m), 7.15 (1H, d, J=8.2 Hz), 6.36 (1H, d), 5.59 (1H, s), 4.01-4.10 (2H, m), 3.91-4.01 (2H, m), 3.69-3.82 (4H, m), 3.51-3.63 (2H, m), 3.11-3.19 (3H, m), 2.97 (4H, d, J=4.7 Hz), 2.25-2.33 (3H, m), 2.10-2.24 (2H, m), 1.89 (1H, d), 1.80 (1H, d). Mass Spectrum (ESI) m/e=588 (M+1).

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. washwashed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine
  4. dry with materialthe organic layer dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-6bdf1b68574a4cee9daebbd92eb5d40d
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…