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

HRID 1618706Notes

Reaction equation

HRID 1618706 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][C:15]=2[S:20]([CH3:23])(=[O:22])=[O:21])[C:3]=1[CH3:24].[O:25]1[CH2:30][CH2:29][N:28]([C:31]2[CH:32]=[C:33]3[NH:39][CH2:38][C:37]4([CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[C:34]3=[N:35][CH:36]=2)[CH2:27][CH2:26]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:39]1[C:33]3[C:34](=[N:35][CH:36]=[C:31]([N:28]4[CH2:29][CH2:30][O:25][CH2:26][CH2:27]4)[CH:32]=3)[C:37]3([CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH2:38]1)=[C:3]([CH3:24])[C:4]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20]([CH3:23])(=[O:22])=[O:21])=[N:5]2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310374-Chloro-5,7-difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinolineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672846931'-(5,7-Difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-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-(2-(methylsulfonyl)phenyl)quinoline (50 mg, 0.14 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (44.9 mg, 0.16 mmol), XPhos precatalyst (20.1 mg, 0.027 mmol), sodium tert-butoxide (32.7 mg, 0.34 mmol), and toluene (1.5 mL) at 95° C. for 18 h. Purification by reverse-phase HPLC (0-70% acetonitrile in water) gave 1′-(5,7-difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-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 7.62-7.76 (1H, m), 7.24-7.33 (1H, m), 7.13-7.23 (1H, m), 6.98-7.09 (2H, m), 6.87-6.98 (1H, m), 6.48-6.60 (1H, m), 5.42-5.51 (1H, m), 3.67-3.76 (1H, m), 3.50-3.67 (2H, m), 3.20-3.28 (4H, m), 2.94-3.14 (2H, m), 2.59-2.65 (1H, m), 2.48-2.59 (6H, m), 1.71-1.88 (2H, m), 1.50-1.55 (1H, m), 1.38-1.46 (2H, m), 1.23-1.38 (1H, m), 1.07-1.19 (1H, m), 0.70-0.75 (1H, m). Mass Spectrum (ESI) m/e=607.0 (M+1).

Workup

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

Sources & evidence

ORD record
ord-c0c0cd0f0db74e77be4f165c5620baa5
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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