Triethylamine → (1R,6S)Biphenyl-2-yl-(8-quinoxalin-2-yl-3,8-diaza-bicyclo[4.2.0]oct-3-yl)-methanone

HRID 1193130Notes

Reaction equation

HRID 1193130 reaction equation
[C@@H:1]12[N:8]([C:9]3[CH:18]=[N:17][C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH2:7][C@@H:6]1[CH2:5][CH2:4][NH:3][CH2:2]2.[C:19]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:20]([C:25](Cl)=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=1.CCN(CC)CC>C(Cl)Cl>[C:19]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]([N:3]1[CH2:4][CH2:5][C@@H:6]2[C@@H:1]([N:8]([C:9]3[CH:18]=[N:17][C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH2:7]2)[CH2:2]1)=[O:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12563768[1,1'-Biphenyl]-2-carbonyl chlorideHCID 68156918(1R,6S)-2-(3,8-diaza-bicyclo[4.2.0]oct-8-yl)quinoxaline

Product 1

HCID 68157237(1R,6S)Biphenyl-2-yl-(8-quinoxalin-2-yl-3,8-diaza-bicyclo[4.2.0]oct-3-yl)-methanoneYield 119.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (1R,6S)-2-(3,8-diaza-bicyclo[4.2.0]oct-8-yl)quinoxaline (179 mg, 0.745 mmol), biphenyl-2-carbonyl chloride (210 mg, 0.97 mmol), Et3N (196 mg, 1.95 mmol) was stirred into DCM (7.0 mL) for 18 h at room temperature. Then reaction mixture was diluted with more DCM (25 mL) and washed successively with 1N aq. NaOH (5 mL) and water (2×15 mL). The organic phase was concentrated under reduced pressure. The crude residue was purified on HPLC (basic system) to yield pure title compound (373 mg, 99%). MS (ESI) mass calcd. for C27H24N4O, 420.52; m/z found, 421.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.00-7.32 (m, 11H), 7.29-7.18 (m, 1H), 6.75 (dd, J=9.9, 4.2, 2H), 4.70-4.42 (m, 1H), 4.30-3.90 (m, 3H), 3.8-3.74 (m, 0.66H), 3.51-3.30 (m, 1.35H), 3.13-3.03 (m, 0.5H), 2.90-2.80 (m, 0.5H), 2.68-2.51 (m, 0.5H), 1.96-1.68 (m, 2H), 1.59-1.43 (m, 0.5H).

Workup

  1. customThen reaction mixture
  2. washwashed successively with 1N aq. NaOH (5 mL) and water (2×15 mL)
  3. concentrationThe organic phase was concentrated under reduced pressure
  4. customThe crude residue was purified on HPLC (basic system)

Sources & evidence

ORD record
ord-88a58950d0bf4a63a4d19a4e45944643
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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