Sodium Carbonate → 4-(ethoxyamino)-6-[1-(3-pyridyl)pyrazol-4-yl]-1H-1,5-naphthyridin-2-one

HRID 1478545Notes

Reaction equation

HRID 1478545 reaction equation
C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:15]2[CH:16]=[N:17][N:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[CH:19]=2)O1.Br[C:28]1[N:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33](=[O:38])[CH:32]=[C:31]2[NH:39][O:40][CH2:41][CH3:42]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C.O.C(#N)C>[CH2:41]([O:40][NH:39][C:31]1[C:30]2[C:35](=[CH:36][CH:37]=[C:28]([C:15]3[CH:16]=[N:17][N:18]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)[CH:19]=3)[N:29]=2)[NH:34][C:33](=[O:38])[CH:32]=1)[CH3:42]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 574162183-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)pyridineHCID 900431286-bromo-4-(ethoxyamino)-1H-1,5-naphthyridin-2-one

Product 1

HCID 900440984-(ethoxyamino)-6-[1-(3-pyridyl)pyrazol-4-yl]-1H-1,5-naphthyridin-2-one

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To Na2CO3 (151 mg, 1.41 mmol) was added water (1.5 ml) and acetonitrile (2 ml) and the solution was degassed for 5 min with argon. 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]pyridine (84 mg, 0.31 mmol), 6-bromo-4-(ethoxyamino)-1H-1,5-naphthyridin-2-one (80 mg, 0.28 mmol) and Pd(dppf)Cl2 (10 mg, 0.014 mmol) were added sequentially followed by addition of acetonitrile (2 ml). The mixture was stirred at 100° C. for 15 h then allowed to cool to ambient temperature. Water and ethyl acetate were added then the phases were separated. The aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Purification by chromatography afforded of 4-(ethoxyamino)-6-[1-(3-pyridyl)pyrazol-4-yl]-1H-1,5-naphthyridin-2-one.

Workup

  1. customthe solution was degassed for 5 min with argon
  2. temperatureto cool to ambient temperature
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. dry with materialthe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography

Sources & evidence

ORD record
ord-f56a2a60e36e4a8c9b8b3faea3cbdef6
Source dataset
uspto-grants-2016_08
Patent number
US09403845B2

Reaction notes

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