1,2-Dichloroethane → N-((3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methyl)-3-methylenecyclobutanecarboxamide

HRID 386229Notes

Reaction equation

HRID 386229 reaction equation
[Cl:1][C:2]1[C:3]([CH:8]([NH2:25])[C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[CH:14][C:15]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:16]3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH2:40]=[C:41]1[CH2:44][CH:43]([C:45](O)=[O:46])[CH2:42]1>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH:8]([NH:25][C:45]([CH:43]2[CH2:44][C:41](=[CH2:40])[CH2:42]2)=[O:46])[C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[CH:14][C:15]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:16]3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 274753-Methylenecyclobutanecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 51051365(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine

Product 1

HCID 53629057N-((3-chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methyl)-3-methylenecyclobutanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

C-(3-Chloro-pyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine (690 mg, 1.99 mmol) was dissolved in 6.0 mL of CH2Cl2 followed by the addition of EDC (600 mg, 2.98 mmol) and HOBT (300 mg, 1.99 mmol). 3-Methylenecyclobutanecarboxylic acid (300 mg, 2.59 mmol) was dissolved in 1.0 mL of CH2Cl2 and added to the homogenous reaction mixture. After 24 h the reaction was concentrated in vacuo and dissolved in EtOAc and the organic layer was washed with sat. NaHCO3. The organic layer was washed with H2O and brine. The organic layers where combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc: Hex] to obtain the desired product as a white fluffy solid; 1H NMR (400 MHz, CDCl3): δ=2.82-2.92 (m, 2H), 2.99-3.06 (m, 2H), 4.77-4.80 (m, 2H), 6.81 (d, 1H, J=7.8 Hz), 7.45-7.54 (m, 3H), 7.83-7.88 (m, 3H), 8.10 (d, 2H, J=7.1 Hz), 8.22-8.23 (brm, 1H), 8.39 (d, 1H, J=1.79 Hz), 8.59 (d, 1H, J=2.5 Hz); MS (ES+): 440.93 (M+1), 442.91 (M+3).

Workup

  1. additionadded to the homogenous reaction mixture
  2. concentrationAfter 24 h the reaction was concentrated in vacuo
  3. dissolutiondissolved in EtOAc
  4. washthe organic layer was washed with sat. NaHCO3
  5. washThe organic layer was washed with H2O and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel column chromatography [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc: Hex]

Sources & evidence

ORD record
ord-a6b77154e57049c593ab053b6c230514
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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