Triphenylphosphine → Ethyl 2-(3-(6-chloropyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazin-2-yl)acetate

HRID 718609Notes

Reaction equation

HRID 718609 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:13]=[C:14]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.Br[C:23]1[CH:24]=[CH:25][C:26]([Cl:29])=[N:27][CH:28]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])=O.[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:29][C:26]1[N:27]=[CH:28][C:23]([C:13]2[N:9]3[N:10]=[CH:11][CH:12]=[C:7]([N:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)[C:8]3=[N:15][C:14]=2[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 27344145-Bromo-2-chloropyridineHCID 117728782Ethyl 2-(8-morpholinoimidazo[1,2-b]pyridazin-2-yl)acetate

Product 1

HCID 117728649Ethyl 2-(3-(6-chloropyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazin-2-yl)acetate

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
110 °C

Procedure

Compound 28c (867 mg, 2.99 mmol), 5-bromo-2-chloropyridine (888 mg, 4.48 mmol), Pd(OAc)2 (46.9 mg, 0.209 mmol), PPh3 (54.8 mg, 0.209 mmol), and KOAc (879 mg, 8.95 mmol) were placed in a 40 mL vial equipped with a stir bar and then the vial was evacuated and backflushed with argon. Dry DMA (10 mL) was added via syringe and then the mixture was heated to 110° C. and stirred for 16 h. The reaction was cooled to rt, diluted with EtOAc (30 mL), and filtered. The solids were washed with EtOAc (30 mL) and then the combined filtrates were washed with water (2×20 mL) and brine (20 mL). The organic phase was dried over Na2SO4 and filtered, and then the solvent was removed under reduced pressure. The crude product was chromatographed on a 40 g SiO2 pre-packed column eluting with 0-60% EtOAc/DCM to afford compound 28d. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.68 (d, J=2.2 Hz, 1H), 8.07 (dd, J=8.3, 2.4 Hz, 1H), 8.00 (d, J=5.6 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 6.11 (d, J=5.6 Hz, 1H), 4.18 (q, J=7.2 Hz, 2H), 3.96-4.03 (m, 4H), 3.89-3.95 (m, 4H), 3.84 (s, 2H), 1.26 (t, J=7.1 Hz, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C19H20ClN5O3: 402.1 (M+H). Found: 402.1.

Workup

  1. customvial equipped with a stir bar
  2. customthe vial was evacuated
  3. additionDry DMA (10 mL) was added via syringe
  4. temperatureThe reaction was cooled to rt
  5. additiondiluted with EtOAc (30 mL)
  6. filtrationfiltered
  7. washThe solids were washed with EtOAc (30 mL)
  8. washthe combined filtrates were washed with water (2×20 mL) and brine (20 mL)
  9. dry with materialThe organic phase was dried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure
  12. customThe crude product was chromatographed on a 40 g SiO2 pre-packed column
  13. washeluting with 0-60% EtOAc/DCM

Sources & evidence

ORD record
ord-0a6620e4bb8e433fbfb52aee8add7f54
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

Loading…