2-Methylbenzylamine → 9-[(Naphthalen-1-ylmethyl)-amino]-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029091Notes

Reaction equation

HRID 1029091 reaction equation
Cl[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.[CH3:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][NH2:21].[CH:26]1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)[CH2:31]CCC[CH2:27]1.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]1([CH2:20][NH:21][C:2]2[CH:16]=[CH:15][C:5]3[C:6](=[O:14])[NH:7][C:8]4[C:13]([C:4]=3[CH:3]=2)=[CH:12][CH:11]=[CH:10][N:9]=4)[C:18]2[C:25](=[CH:27][CH:26]=[CH:31][CH:17]=2)[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 69932-MethylbenzylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 581682989-chloro-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 581683169-[(Naphthalen-1-ylmethyl)-amino]-5H-benzo[c][1,8]naphthyridin-6-oneYield 355.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

9-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (50 mg, 0.22 mmol), 2-methylbenzylamine (53 mg, 0.43 mmol), palladium(II) acetate (2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (10 mg, 0.02 mmol), and sodium tert-butoxide (63 mg, 0.65 mmol) were suspended in dioxane (2 mL), and stirred overnight at 100° C. The reaction mixture was concentrated, diluted with H2O/EtOAc, and filtered. The precipitate was washed with EtOAc/H2O and purified via prep-LC-MS. The purified product was converted to the HCl salt via dissolving in MeOH, addition of 1 M HCl/ether, and concentration. The HCl salt was triturated in CH2Cl2, filtered, washed with CH2Cl2, and dried under vacuum to provide 45 (25 mg, 33% yield) as a yellow solid. LC-MS (M+H=316, obsd.=316). 1H NMR (400 MHz, d6-DMSO): δ 11.50 (s, 1H), 8.59 (dd, 1H), 8.42 (dd, 1H), 8.00 (d, 1H), 7.41 (d, 1H), 7.33 (dd, 1H), 7.22 (m, 4H), 6.98 (dd, 1H), 4.45 (s, 2H), 2.37 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with H2O/EtOAc
  3. filtrationfiltered
  4. washThe precipitate was washed with EtOAc/H2O
  5. custompurified via prep-LC-MS
  6. dissolutionvia dissolving in MeOH
  7. additionaddition of 1 M HCl/ether, and concentration
  8. customThe HCl salt was triturated in CH2Cl2
  9. filtrationfiltered
  10. washwashed with CH2Cl2
  11. customdried under vacuum

Sources & evidence

ORD record
ord-3d1aaba4539747f297e5eac656523128
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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