Morpholine → HCID 72188527, compound

HRID 1773484Notes

Reaction equation

HRID 1773484 reaction equation
Br[C:2]1[N:30]=[CH:29][CH:28]=[CH:27][C:3]=1[C:4]([NH:6][C@H:7]([C:9]1[N:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:11](=[O:20])[C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[CH3:8])=[O:5].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>O1CCOCC1>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:12]=1[C:11](=[O:20])[N:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:9]([C@@H:7]([NH:6][C:4](=[O:5])[C:3]1[CH:27]=[CH:28][CH:29]=[N:30][C:2]=1[N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[CH3:8])=[CH:18]2

Participants

4

Reactant 2

HCID 8083MorpholineHCID 86698493HCID 86698493, compound

Product 1

HCID 72188527HCID 72188527, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of (S)-2-bromo-N-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)nicotinamide (52) (150 mg, 0.31 mmol) in anhydrous 1,4-dioxane (3 mL) in a sealed tube, morpholine (1 mL, excess amount) was added and the resulting mixture was stirred at 140° C. for 6 h. The mixture was allowed to cool to RT and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH-DCM) followed by prep-TLC plate purification (10% MeOH-DCM) to afford the product (S)-N-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)-2-morpholinonicotinamide (compound 53). ESI-MS m/z: 489.0 [M+H]+.

Workup

  1. temperatureto cool to RT
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH-DCM)
  8. customfollowed by prep-TLC plate purification (10% MeOH-DCM)

Sources & evidence

ORD record
ord-a63c4c4122e146cfb4156d4dd135d395
Source dataset
uspto-grants-2016_02
Patent number
US09255108B2

Reaction notes

Loading…