Hydrochloric Acid → 3-(5-amino-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

HRID 2243852Notes

Reaction equation

HRID 2243852 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([C:8]2[C:9](=[O:20])[N:10]([CH3:19])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)[CH:7]=1.[C:22]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Al](C)C.Cl>O1CCOCC1.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([C:8]2[C:9](=[O:20])[N:10]([CH3:19])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([CH3:22])[CH:12]=3)[CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 16682925TrimethylaluminumHCID 598338283-(5-amino-2-methylphenyl)-7-chloro-1-methyl-1,6-naphthyridin-2(1H)-one

Product 1

HCID 592123103-(5-amino-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-(5-amino-2-methylphenyl)-7-chloro-1-methyl-1,6-naphthyridin-2-one 8 (0.53 mmol) in dioxane (3 mL) is added triphenylphosphine (0.08 mmol), Pd2(dba)3 (16 umol) and trimethylaluminum (0.8 mL of a 2.0 molar solution in toluene). The mixture is degassed for 10 minutes then the reaction vial sealed and heated via microwave for 10 minutes at 150° C. The reaction is cooled to rt and poured into 1M HCl (30 mL) and washed with EtOAc. The aqueous layer is made basic with 3M NaOH and extracted with EtOAc (3×20 mL). The combined organic layers are dried over magnesium sulfate, filtered and reduced to dryness. The crude yellow oil is purified by flash chromatography on silica with dichloromethane 3-5% MeOH as eluant to yield a yellow glassy solid 15. 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.63 (s, 1H), 7.08 (s, 1H), 7.05 (d, J=8.4 Hz, 1H), 6.65 (dd, J=8.4, 2.4 Hz, 1H), 6.57 (d, J=2.4 Hz, 1H), 3.72 (s, 3H), 2.70 (s, 3H), 2.11 (s, 3H). MS (m/z) (M+1)+: 280.1.

Workup

  1. customThe mixture is degassed for 10 minutes
  2. customthe reaction
  3. customvial sealed
  4. temperatureThe reaction is cooled to rt
  5. washwashed with EtOAc
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialThe combined organic layers are dried over magnesium sulfate
  8. filtrationfiltered
  9. customThe crude yellow oil is purified by flash chromatography on silica with dichloromethane 3-5% MeOH as eluant

Sources & evidence

ORD record
ord-81d45861bea94b889f5df7c817820a46
Source dataset
uspto-grants-2010_03
Patent number
US07678792B2

Reaction notes

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