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

HRID 2061158Notes

Reaction equation

HRID 2061158 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) was added triphenylphosphine (0.08 mmol), Pd2(dba)3 (16 umol) and trimethylaluminum (0.8 mL of a 2.0 M solution in toluene). The mixture was degassed for 10 minutes. The reaction vial was sealed and heated via microwave for 10 minutes at 150° C. The reaction was cooled to rt and poured into 1M HCl (30 mL) and washed with EtOAc. The aqueous layer was made basic with 3M NaOH and extracted with EtOAc (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and reduced to dryness by evaporation. The crude yellow oil was purified by flash chromatography on silica with DCM containing 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 was degassed for 10 minutes
  2. customThe reaction
  3. customvial was sealed
  4. temperatureThe reaction was cooled to rt
  5. washwashed with EtOAc
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. customreduced to dryness by evaporation
  10. customThe crude yellow oil was purified by flash chromatography on silica with DCM containing 3-5% MeOH as eluant

Sources & evidence

ORD record
ord-b2dd2f9607a2426cae8563f17f123d0a
Source dataset
uspto-grants-2012_10
Patent number
US08278452B2

Reaction notes

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