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

HRID 1618702Notes

Reaction equation

HRID 1618702 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:19].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:27]=[C:28]3[NH:34][CH2:33][C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[C:29]3=[N:30][CH:31]=2)[CH2:22][CH2:21]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]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([N:34]1[C:28]3[C:29](=[N:30][CH:31]=[C:26]([N:23]4[CH2:24][CH2:25][O:20][CH2:21][CH2:22]4)[CH:27]=3)[C:32]3([CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH2:33]1)=[C:3]([CH3:19])[C:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:5]2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596312094-Chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672852951'-(5-Fluoro-3-methyl-2-(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-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (29.7 mg, 0.11 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (30 mg, 0.11 mmol), XPhos precatalyst (7 mg, 0.01 mmol) and sodium tert butoxide (20.9 mg, 0.22 mmol) in toluene (3 mL) at 90° C. for 2 h. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(5-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (500 MHz, chloroform-d) δ ppm 8.65-8.84 (1H, m), 8.02-8.07 (1H, m), 7.86-7.96 (2H, m), 7.64 (1H, td, J=8.1, 5.4 Hz), 7.56 (1H, d, J=2.2 Hz), 7.42 (1H, ddd, J=6.8, 4.9, 2.0 Hz), 7.14-7.21 (1H, m), 5.77 (1H, d, J=2.2 Hz), 4.08-4.18 (2H, m), 3.91-4.02 (2H, m), 3.70-3.80 (4H, m), 3.51-3.63 (2H, m), 2.95-3.05 (4H, m), 2.42-2.45 (3H, s), 2.35-2.40 (1H, m), 2.28 (1H, ddd, J=13.7, 11.5, 4.4 Hz), 1.85 (1H, ddd, J=13.6, 1.5, 1.3 Hz), 1.70-1.76 (1H, m). Mass Spectrum (ESI) m/e=512.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-d6297e5f434843288c6b79e4ccea3806
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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