Benzylamine → HCID 44138603, compound

HRID 1620218Notes

Reaction equation

HRID 1620218 reaction equation
Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:14][CH3:15])[CH:8]=2)[N:3]=1.[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[CH2:16]([NH:23][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:14][CH3:15])[CH:8]=2)[N:3]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 6890792-Chloro-6-methoxyquinoline-3-carbaldehyde

Product 1

HCID 44138603HCID 44138603, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

To a stirred solution of 2-chloro-6-methoxyquinoline-3-carbaldehyde (2.00 g, 9.02 mmol) in THF (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added benzylamine (4.88 mL, 90.20 mmol) and the reaction mixture was stirred for 1.5 h at 160° C. then 45 min at 180° C. under microwave irradiation. After cooling to RT, the volatiles were removed at 40° C. under vacuum and the resulting yellow oil was taken up in a mixture of THF:1 N aq. HCl=1:1 (50 mL) and stirred for 1 h at RT. The volatiles were then removed at 40° C. under vacuum and the residue was then neutralised with a saturated NaHCO3 aqueous solution before extraction with CH2Cl2 (100 mL). The organic phase was washed with brine (20 mL), dried over MgSO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 75:25) provided a mixture of the desired product and its benzyl imine derivative. This mixture was taken up in a mixture of THF:1 N aq. HCl=1:1 (20 mL) and stirred for 2 h at RT. The volatiles were then removed at 40° C. under vacuum and the residue was then neutralised with a saturated NaHCO3 aqueous solution before extraction with CH2Cl2 (100 mL). The organic phase was washed with brine (20 mL), dried over MgSO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 75:25) gave, after evaporation and drying, 2-(benzylamino)-6-methoxyquinoline-3-carbaldehyde SLA 41002 as a yellow solid (0.431 g, 16% yield).

Workup

  1. custom45 min at 180° C. under microwave irradiation
  2. temperatureAfter cooling to RT
  3. customthe volatiles were removed at 40° C. under vacuum
  4. additionthe resulting yellow oil was taken up in a mixture of THF
  5. stirring1 N aq. HCl=1:1 (50 mL) and stirred for 1 h at RT
  6. customThe volatiles were then removed at 40° C. under vacuum
  7. extractionthe residue was then neutralised with a saturated NaHCO3 aqueous solution before extraction with CH2Cl2 (100 mL)
  8. washThe organic phase was washed with brine (20 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated at 40° C. under vacuum
  12. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 75:25)
  13. customprovided

Sources & evidence

ORD record
ord-a121715a35d94a539382533d29dbe6db
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

Loading…