Sodium Carbonate → (R)-4-Methyl-6-phenyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 925643Notes

Reaction equation

HRID 925643 reaction equation
Br[C:2]1[C:10]2[N:9]3[C@H:11]([CH3:16])[CH2:12][NH:13][C:14](=[O:15])[C:8]3=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:16][C@H:11]1[N:9]2[C:10]3[C:2]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:3][CH:4]=[CH:5][C:6]=3[CH:7]=[C:8]2[C:14](=[O:15])[NH:13][CH2:12]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 66827Phenylboronic AcidHCID 68890146(R)-6-bromo-4-methyl-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

Product 1

HCID 73336183(R)-4-Methyl-6-phenyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 87%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (R)-6-bromo-4-methyl-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one [CAS No. 396075-75-5] (69.8 mg, 0.25 mmol) and commercially available phenylboronic acid (39.6 mg, 0.325 mmol) in 1,2-dimethoxyethane (1.67 ml) and 2M sodium carbonate solution (416 μl, 832 μmol) was purged with argon in an ultrasonic bath for 5 min. Then triphenylphosphine (13.1 mg, 50.0 μmol) and palladium(II)acetate (5.61 mg, 25.0 μmol) were added at room temperature, and afterwards the reaction mixture was allowed to stir for 2 h at 85° C. The reaction mixture was cooled to room temperature, poured into water (20 ml) and extracted with dichloromethane (2×20 ml). The combined organic layers were washed with brine (1×20 ml), dried (MgSO4) and evaporated. The crude material (70 mg) was purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (20-80%)] and subsequent trituration with diethyl ether (0.5 ml) and heptane (10 ml) to yield the title compound as a grey solid (60 mg, 87%), MS (ISN) m/z=277.2 [(M+H)+], mp 239° C.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (2×20 ml)
  3. washThe combined organic layers were washed with brine (1×20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude material (70 mg) was purified by flash chromatography on silica gel [dichloromethane-dichloromethane/MeOH 9:1 (20-80%)] and subsequent trituration with diethyl ether (0.5 ml) and heptane (10 ml)

Sources & evidence

ORD record
ord-6c3bf5afd3c94d418950977161b8cced
Source dataset
uspto-grants-2016_03
Patent number
US09284321B2

Reaction notes

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