Sodium t-butoxide → 1'-(7-Fluoro-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 1618718Notes

Reaction equation

HRID 1618718 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:20].[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:28]=[C:29]3[NH:35][CH2:34][C:33]4([CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[C:30]3=[N:31][CH:32]=2)[CH2:23][CH2:22]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:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:35]3[C:29]4[C:30](=[N:31][CH:32]=[C:27]([N:24]5[CH2:25][CH2:26][O:21][CH2:22][CH2:23]5)[CH:28]=4)[C:33]4([CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[CH2:34]3)=[C:3]([CH3:20])[C:4]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=3)=[N:5]2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310864-Chloro-7-fluoro-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 672846091'-(7-Fluoro-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-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (50 mg, 0.17 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (48.0 mg, 0.17 mmol), sodium tert-butoxide (33.5 mg, 0.35 mmol), XPhos precatalyst (26 mg, 0.035 mmol), and toluene (1.7 mL) at 90° C. for 18 h. Purification by reverse-phase HPLC (0-70% acetonitrile in water) gave 1′-(7-fluoro-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] as a yellow film. 1H NMR (400 MHz, chloroform-d) δ ppm 8.60 (1H, d, J=5.1 Hz), 7.87 (1H, dd, J=9.8, 2.5 Hz), 7.69-7.75 (2H, m), 7.59-7.61 (1H, m), 7.29-7.36 (1H, m), 7.23-7.27 (1H, m), 5.89 (1H, s), 4.14-4.21 (2H, m), 4.02 (2H, s), 3.70-3.81 (4H, m), 3.50-3.62 (2H, m), 2.95-3.09 (4H, m), 2.51 (4H, s), 2.45 (1H, s), 2.38 (3H, s), 1.81-1.90 (1H, m), 1.70-1.81 (1H, m). Mass Spectrum (ESI) m/e=526.2 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC (0-70% acetonitrile in water)

Sources & evidence

ORD record
ord-4842430878254ead8b798a480b149129
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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