Sodium t-butoxide → 1'-(5,7-Difluoro-3-methyl-2-(4-methyl-2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618699Notes

Reaction equation

HRID 1618699 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]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=2)[C:3]=1[CH3:21].[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[C:30]3[NH:36][CH2:35][C:34]4([CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[C:31]3=[N:32][CH:33]=2)[CH2:24][CH2:23]1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[F:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([N:36]1[C:30]3[C:31](=[N:32][CH:33]=[C:28]([N:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)[CH:29]=3)[C:34]3([CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH2:35]1)=[C:3]([CH3:21])[C:4]([C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=1)=[N:5]2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596311504-Chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672845891'-(5,7-Difluoro-3-methyl-2-(4-methyl-2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (45 mg, 0.148 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (48.8 mg, 0.177 mmol), XPhos precatalyst (10.9 mg, 0.015 mmol), sodium tert-butoxide (28.4 mg, 0.295 mmol), and toluene (1.6 mL) at 95° C. for 24 h. Purification by column chromatography (basic alumina, 0-30% EtOAc in hexanes) gave 1′-(5,7-difluoro-3-methyl-2-(4-methyl-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 8.60 (1H, d, J=5.1 Hz), 7.68-7.74 (2H, m), 7.54-7.58 (1H, m), 7.21-7.27 (1H, m), 7.02 (1H, t, J=3.1 Hz), 5.78 (1H, s), 4.14 (2H, td, J=11.6, 3.9 Hz), 3.92-4.00 (1H, m), 3.71-3.84 (5H, m), 3.49-3.62 (2H, m), 2.98-3.08 (4H, m), 2.51 (3H, s), 2.37-2.42 (3H, m), 1.83 (1H, d, J=13.9 Hz), 1.68-1.78 (1H, m), 1.28-1.34 (2H, m). Mass Spectrum (ESI) m/e=544.1 (M+1).

Workup

  1. customPrepared
  2. customPurification by column chromatography (basic alumina, 0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8b25b603642a4b15b230b876806c5c43
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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