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

HRID 1618763Notes

Reaction equation

HRID 1618763 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:3]=1[CH3:19].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:27]=[C:28]3[NH:34][CH2:33][C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[C:29]3=[N:30][CH:31]=2)[CH2:22][CH2:21]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:18][C:14]1[CH:13]=[C:12]([C:4]2[C:3]([CH3:19])=[C:2]([N:34]3[C:28]4[C:29](=[N:30][CH:31]=[C:26]([N:23]5[CH2:24][CH2:25][O:20][CH2:21][CH2:22]5)[CH:27]=4)[C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:33]3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=[CH:16][CH: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 672853774-Chloro-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine

Product 1

HCID 672852851'-(2-(3-Fluorophenyl)-3-methyl-1,8-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 using 4-chloro-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine (49.5 mg, 0.182 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (50 mg, 0.182 mmol), sodium tert-butoxide (34.9 mg, 0.363 mmol) and XPhos precatalyst (13.35 mg, 0.018 mmol) in toluene (4 mL) for 2 hours at 110° C. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(2-(3-fluorophenyl)-3-methyl-1,8-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 9.13 (1H, dd, J=4.3, 2.0 Hz), 8.13 (1H, dd, J=8.2, 2.0 Hz), 7.66 (1H, d, J=2.3 Hz), 7.42-7.54 (4H, m), 7.15-7.23 (1H, m), 5.79 (1H, d, J=2.3 Hz), 4.14-4.21 (2H, m), 3.71-3.82 (4H, m), 3.56-3.65 (2H, m), 2.95-3.06 (4H, m), 2.30-2.43 (5H, m), 1.62-1.89 (4H, m). Mass Spectrum (ESI) m/e=512.2 (M+1).

Workup

  1. customPrepared
  2. customfor 2 hours
  3. customat 110° C
  4. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-06c2ddfeab17432d8dc652c0d37de422
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…