Sodium t-butoxide → 1-(7-fluoro-3-methyl-4-(6'-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridin]-1'(2'H)-yl)-2-quinolinyl)-2-pyrrolidinone

HRID 1618733Notes

Reaction equation

HRID 1618733 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]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[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:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:34]3[C:28]4[C:29](=[N:30][CH:31]=[C:26]([N:23]5[CH2:24][CH2:25][O:20][CH2:21][CH2:22]5)[CH:27]=4)[C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:33]3)=[C:3]([CH3:19])[C:4]([N:13]3[CH2:17][CH2:16][CH2:15][C:14]3=[O:18])=[N:5]2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596313861-(4-Chloro-7-fluoro-3-methylquinolin-2-yl)pyrrolidin-2-oneHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672847341-(7-fluoro-3-methyl-4-(6'-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridin]-1'(2'H)-yl)-2-quinolinyl)-2-pyrrolidinone

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)pyrrolidin-2-one (50 mg, 0.179 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (49.4 mg, 0.179 mmol), XPhos precatalyst (26.5 mg, 0.036 mmol), sodium tert-butoxide (34.5 mg, 0.359 mmol), and toluene (1.5 mL) at 95° C. for 2 h. Purification by reverse phase HPLC (0-70% acetonitrile in water) gave 1-(7-fluoro-3-methyl-4-(6′-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-1′(2′H)-yl)-2-quinolinyl)-2-pyrrolidinone. 1H NMR (400 MHz, chloroform-d) δ ppm 7.76 (1H, dd, J=9.1, 6.0 Hz), 7.61-7.69 (2H, m), 7.21-7.26 (1H, m), 5.89 (1H, s), 4.13 (4H, d, J=6.8 Hz), 4.04-4.10 (1H, m), 3.93 (1H, d, J=9.6 Hz), 3.70-3.83 (4H, m), 3.51-3.66 (2H, m), 3.03 (4H, dd, J=5.7, 3.7 Hz), 2.65 (2H, t, J=8.0 Hz), 2.24-2.42 (4H, m), 2.18 (3H, s), 1.83 (1H, d, J=13.7 Hz), 1.73 (1H, d, J=13.3 Hz). Mass Spectrum (ESI) m/e=518.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-898ca1309be54e0fa43922748c96dd02
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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