Tetrahydrofuran → 8-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

HRID 872002

Reaction equation

HRID 872002 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([CH2:18][N:19]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[O:43][CH3:44])C(OCC3C4C=CC=CC=4C4C3=CC=CC=4)=O)=[C:16]3[C:11]([NH:12][C:13]([CH3:48])([CH3:47])[C:14](=[O:46])[N:15]3[CH3:45])=[CH:10][CH:9]=2)=[C:4]([O:49][CH3:50])[CH:3]=1.[CH2:51]([N:53](CC)[CH2:54]C)C.Cl.[Cl-].[O:60]1[CH2:64][CH2:63][CH2:62][CH2:61]1>ClCCl>[CH3:44][O:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[NH:19][CH2:18][C:17]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][C:64]([C:63]3[CH:51]=[N:53][CH:54]=[CH:61][CH:62]=3)=[O:60])=[CH:3][C:4]=2[O:49][CH3:50])=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]([CH3:45])[C:14](=[O:46])[C:13]([CH3:48])([CH3:47])[NH:12]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 6410751Hydrogen chloride dimerHCID 583372217-(4-Hydroxy-2-methoxyphenyl)-8-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 576718608-(2-Methoxyphenylaminomethyl)-7-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-oneYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-(4-Hydroxy-2-methoxyphenyl)-8-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Compound No. 13-1, 30.0 mg, 0.0448 mmol) was dissolved in mixed solvent of tetrahydrofuran (1 mL) and dichloromethane (1 mL), and triethylamine (25 μL, 0.18 mmol) and nicotynoyl chloride hydrochloride (12.0 mg, 0.0674 mmol) were added successively. After the reaction mixture was stirred for 40 minutes at room temperature, it was purified by silica gel column chromatography (hexane-ethyl acetate). The obtained colorless amorphous product was dissolved in N,N-dimethylformamide (1 mL) and piperidine (50 μL) was added thereto. After the reaction mixture was stirred for 20 minutes at room temperature, it was diluted with ethyl acetate (50 mL). The mixture was washed with water (50 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled compound (13.0 mg) as a colorless solid. (Yield 52%)

Workup

  1. additionwere added successively
  2. customit was purified by silica gel column chromatography (hexane-ethyl acetate)
  3. dissolutionThe obtained colorless amorphous product was dissolved in N,N-dimethylformamide (1 mL)
  4. additionpiperidine (50 μL) was added
  5. stirringAfter the reaction mixture was stirred for 20 minutes at room temperature
  6. additionit was diluted with ethyl acetate (50 mL)
  7. washThe mixture was washed with water (50 mL) and saturated brine (50 mL) successively
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-cef1495e08044299bf14d03870ec8f16
Source dataset
uspto-grants-2015_03
Patent number
US08975256B2

Linked notes

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