Sodium t-butoxide → HCID 67285432, compound

HRID 1618722Notes

Reaction equation

HRID 1618722 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]([N:14]2[CH2:19][CH2:18][O:17][C:16]([CH3:21])([CH3:20])[CH2:15]2)[C:3]=1[CH3:22].[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[C:31]3[NH:37][CH2:36][C:35]4([CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[C:32]3=[N:33][CH:34]=2)[CH2:25][CH2:24]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>[CH3:20][C:16]1([CH3:21])[O:17][CH2:18][CH2:19][N:14]([C:4]2[C:3]([CH3:22])=[C:2]([N:37]3[C:31]4[C:32](=[N:33][CH:34]=[C:29]([N:26]5[CH2:27][CH2:28][O:23][CH2:24][CH2:25]5)[CH:30]=4)[C:35]4([CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[CH2:36]3)[C:11]3[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=3[F:12])[N:5]=2)[CH2:15]1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]HCID 67284943HCID 67284943, compound

Product 1

HCID 67285432HCID 67285432, compound

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by using 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-2,2-dimethylmorpholine (47.5 mg, 0.14 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (40 mg, 0.14 mmol), sodium tert-butoxide and XPhos precatalyst (10.7 mg, 0.01 mmol) in toluene (4 mL) for 2 h at reflux. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(2-(2,2-dimethyl-4-morpholinyl)-5,7-difluoro-3-methyl-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 7.57 (1H, d, J=2.5 Hz), 7.35-7.40 (1H, m), 6.75 (1H, ddd, J=11.8, 8.9, 2.5 Hz), 5.67 (1H, d, J=2.3 Hz), 4.09-4.18 (2H, m), 3.94-4.00 (2H, m), 3.82-3.94 (2H, m), 3.72-3.80 (4H, m), 3.51-3.63 (2H, m), 3.27-3.38 (2H, m), 3.11-3.25 (2H, m), 2.95-3.02 (4H, m), 2.23-2.38 (5H, m), 1.55-1.78 (2H, m), 1.40 (3H, s), 1.37 (3H, s). Mass Spectrum (ESI) m/e=566.2 (M+1).

Workup

  1. customPrepared
  2. customfor 2 h
  3. temperatureat reflux
  4. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-fde1df7470924dfc90ef105805980412
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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