Sodium t-butoxide → 1'-(3-Methyl-2-(pyridin-2-yl)-1,8-naphthyridin-4-yl)-6'-morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618732Notes

Reaction equation

HRID 1618732 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[NH:15][CH2:14][C:13]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:10]3=[N:11][CH:12]=2)[CH2:3][CH2:2]1.Cl[C:22]1[C:31]2[C:26](=[N:27][CH:28]=[CH:29][CH:30]=2)[N:25]=[C:24]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[C:23]=1[CH3:38].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>[CH3:38][C:23]1[C:24]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)=[N:25][C:26]2[C:31]([C:22]=1[N:15]1[C:9]3[C:10](=[N:11][CH:12]=[C:7]([N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH:8]=3)[C:13]3([CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:14]1)=[CH:30][CH:29]=[CH:28][N:27]=2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672846491'-(3-Methyl-2-(pyridin-2-yl)-1,8-naphthyridin-4-yl)-6'-morpholino-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 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (70 mg, 0.254 mmol), 4-chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine (65.0 mg, 0.25 mmol), sodium tert-butoxide (48.9 mg, 0.51 mmol) and XPhos precatalyst (18.7 mg, 0.025 mmol) in toluene (5 mL) for 2 h at 100° C. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(3-methyl-2-(pyridin-2-yl)-1,8-naphthyridin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 9.13 (1H, dd, J=4.1, 2.0 Hz), 8.72 (1H, ddd, J=4.8, 1.8, 1.0 Hz), 8.19 (1H, dt, J=7.8, 1.2 Hz), 8.13 (1H, dd, J=8.4, 2.0 Hz), 7.93 (1H, td, J=7.7, 1.8 Hz), 7.64 (1H, d, J=2.3 Hz), 7.39-7.47 (2H, m), 5.82 (1H, d, J=2.3 Hz), 4.13-4.20 (2H, m), 4.08 (1H, d, J=9.8 Hz), 3.97 (1H, d, J=9.6 Hz), 3.72-3.78 (4H, m), 3.55-3.62 (2H, m), 2.95-3.04 (4H, m), 2.51 (3H, s), 2.20-2.35 (2H, m), 1.74-1.87 (2H, m). Mass Spectrum (ESI) m/e=495.2 (M+1).

Workup

  1. customPrepared
  2. customfor 2 h
  3. customat 100° C
  4. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-377460acf550452ab7bf619e2774ca40
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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