Sodium t-butoxide → HCID 67285490, compound

HRID 1618559Notes

Reaction equation

HRID 1618559 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:3]=1[CH3:20].[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[C:31]3[NH:33][CH2:34][C:35]4([CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:30]3=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.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+]>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:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([N:33]1[C:31]3[C:30](=[CH:29][CH:28]=[C:27]([N:24]4[CH2:23][CH2:22][O:21][CH2:26][CH2:25]4)[CH:32]=3)[C:35]3([CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH2:34]1)=[C:3]([CH3:20])[C:4]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)=[N:5]2

Participants

7

Reactant 4

HCID 23676156Sodium t-butoxideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]HCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 67285490HCID 67285490, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (60.7 mg, 0.21 mmol) (described herein), 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (68.7 mg, 0.25 mmol) (described herein), Pd2dba3 (28.7 mg, 0.031 mmol), 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (29.9 mg, 0.063 mmol), and sodium tert-butoxide (60.2 mg, 0.626 mmol) in toluene (3 mL) was stirred at 100° C. for 22 h, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with saturated aqueous sodium bicarbonate solution, 1 M NaOH, and brine, and the organic layer dried (MgSO4) and concentrated. Chromatography afforded 1-(5,7-difluoro-3-methyl-2-(2-pyridinyl)-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 8.71-8.79 (1H, m), 7.85-7.97 (2H, m), 7.65-7.74 (1H, m), 7.42 (1H, ddd, J=7.0, 5.0, 1.7 Hz), 7.09 (1H, d, J=8.2 Hz), 6.97 (1H, ddd, J=11.6, 8.9, 2.5 Hz), 6.25-6.34 (1H, m), 5.45-5.57 (1H, m), 3.98-4.09 (2H, m), 3.86-3.96 (2H, m), 3.69-3.82 (4H, m), 3.46-3.62 (2H, m), 2.91-3.05 (4H, m), 2.39 (3H, s), 2.06-2.24 (2H, m), 1.83-1.93 (1H, m), 1.72-1.83 (1H, m). Mass Spectrum (ESI) m/e=529 (M+1).

Workup

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

Sources & evidence

ORD record
ord-3bee87ed22d2496eb19fbf600d3ffa8c
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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