Sodium t-butoxide → 1'-(3-Methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-yl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]-pyridine]

HRID 1618738Notes

Reaction equation

HRID 1618738 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:3]=1[CH3:18].[O:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:26]=[C:27]3[NH:33][CH2:32][C:31]4([CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[C:28]3=[N:29][CH:30]=2)[CH2:21][CH2:20]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>[CH3:18][C:3]1[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:5][C:6]2[C:11]([C:2]=1[N:33]1[C:27]3[C:28](=[N:29][CH:30]=[C:25]([N:22]4[CH2:23][CH2:24][O:19][CH2:20][CH2:21]4)[CH:26]=3)[C:31]3([CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[CH2:32]1)=[CH:10][CH:9]=[N:8][CH:7]=2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596313804-Chloro-3-methyl-2-(pyridin-2-yl)-1,7-naphthyridineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672850771'-(3-Methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-yl)-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 using 4-chloro-3-methyl-2-(pyridin-2-yl)-1,7-naphthyridine (70 mg, 0.274 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (75 mg, 0.274 mmol), sodium tert-butoxide (52.6 mg, 0.548 mmol) and XPhos precatalyst (20 mg, 0.027 mmol) with heating in toluene (4 mL) for 2 h at 110° C. Purification by reverse phase HPLC (to 10 50% acetonitrile water) gave 1′-(3-methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-yl)-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 9.60 (1H, d, J=1.0 Hz), 8.75 (1H, dt, J=4.8, 1.5 Hz), 8.55 (1H, d, J=5.9 Hz), 7.92-8.01 (2H, m), 7.65 (1H, d, J=2.3 Hz), 7.51 (1H, dd, J=5.7, 1.0 Hz), 7.43 (1H, ddd, J=6.0, 4.8, 2.9 Hz), 5.84 (1H, d, J=2.3 Hz), 4.12-4.20 (2H, m), 3.93-4.05 (2H, m), 3.71-3.77 (4H, m), 3.52-3.62 (2H, m), 2.95-3.12 (4H, m), 2.47 (3H, s), 2.28-2.43 (2H, m), 1.69-1.88 (2H, m). Mass Spectrum (ESI) m/e=495.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse phase HPLC (to 10 50% acetonitrile water)

Sources & evidence

ORD record
ord-a2d484d229d1437d9063e64e0cd9b9ea
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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