Sodium t-butoxide → HCID 67285595, compound

HRID 1618720Notes

Reaction equation

HRID 1618720 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][N:17]=[C:16]([O:20][CH3:21])[CH: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>[F:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([N:37]1[C:31]3[C:32](=[N:33][CH:34]=[C:29]([N:26]4[CH2:27][CH2:28][O:23][CH2:24][CH2:25]4)[CH:30]=3)[C:35]3([CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[CH2:36]1)=[C:3]([CH3:22])[C:4]([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([O:20][CH3:21])[CH:15]=1)=[N:5]2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 59631439HCID 59631439, compoundHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 67285595HCID 67285595, compound

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 4-chloro-5,7-difluoro-2-(2-methoxypyridin-4-yl)-3-methylquinoline (50 mg, 0.16 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (42.9 mg, 0.16 mmol), sodium tert-butoxide (33.0 mg, 0.34 mmol), XPhos precatalyst (23.0 mg, 0.031 mmol), and toluene (1.7 mL) at 85° C. for 6 h. Purification by reverse-phase HPLC (0-70% acetonitrile in water) gave 1′-(5,7-difluoro-2-(2-methoxy-4-pyridinyl)-3-methyl-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro-[pyran-4,3′-pyrrolo[3,2-b]pyridine] as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.32-8.36 (1H, m), 7.66-7.71 (1H, m), 7.60 (1H, d, J=2.3 Hz), 7.09 (1H, dd, J=5.2, 1.5 Hz), 6.99-7.07 (1H, m), 6.95-6.97 (1H, m), 5.73-5.76 (1H, m), 4.14-4.20 (2H, m), 4.03 (3H, s), 3.96-4.01 (1H, m), 3.89-3.94 (1H, m), 3.74-3.81 (4H, m), 3.52-3.62 (2H, m), 2.98-3.07 (4H, m), 2.31-2.46 (2H, m), 2.27-2.30 (3H, m), 1.78-1.86 (1H, m), 1.67-1.75 (1H, m). Mass Spectrum (ESI) m/e=560.0 (M+1).

Workup

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

Sources & evidence

ORD record
ord-28263c3deec94f31885fd3dccc9a3687
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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