Sodium Carbonate → (rac)-N-[4-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro isoquinolin-8-yl]-propionamide

HRID 530357Notes

Reaction equation

HRID 530357 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.Br[C:24]1[C:33]2[CH2:32][CH2:31][CH2:30][CH:29]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[C:28]=2[CH:27]=[N:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1[C:24]1[C:33]2[CH2:32][CH2:31][CH2:30][CH:29]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[C:28]=2[CH:27]=[N:26][CH:25]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 86679131HCID 86679131, compoundHCID 86685953N-(4-Bromo-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide

Product 1

HCID 71537046(rac)-N-[4-(7-Fluoro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-5,6,7,8-tetrahydro isoquinolin-8-yl]-propionamideYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-9, 168 mg, 0.55 mmol) and (rac)-N-(4-bromo-5,6,7,8-tetrahydro-isoquinolin-8-yl)-propionamide (intermediate B-1) (142 mg, 0.5 mmol) in DMF (3 mL) was purged with argon for 1 min before bis(triphenylphosphine)palladium (II)chloride (38 mg, 0.054 mmol) and 1 N aq. Na2CO3 (2.5 mL) were added. The resulting reaction mixture was purged with argon for 2 min, and heated at 100° C. for 45 min in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc (5 mL) before it was poured into a satd. aq. solution of NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (3×5 mL) and the combined organic layers were washed with water and brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give the title compound (120 mg, 63% yield) as a white solid. MS: 382.3 (M+H)+

Workup

  1. additionwere added
  2. customThe resulting reaction mixture
  3. customwas purged with argon for 2 min
  4. temperatureAfter cooling to room temperature
  5. additionthe reaction mixture was diluted with EtOAc (5 mL) before it
  6. additionwas poured into a satd
  7. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  8. washthe combined organic layers were washed with water and brine
  9. customdried over anhy
  10. filtrationNa2SO4, filtered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-2a4895b82a9f4dfcbc664cbe3e9fe1ff
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

Loading…