Pivaloyl chloride → N-[(3-chloropyrazin-2-yl)-(2-phenylquinolin-7-yl)-methyl]-2,2-dimethylpropionamide

HRID 244098Notes

Reaction equation

HRID 244098 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(N(C(C)C)C(C)C)C.[C:35](Cl)(=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH:8]([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)[NH:25][C:35](=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 51051365(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine

Product 1

HCID 57681060N-[(3-chloropyrazin-2-yl)-(2-phenylquinolin-7-yl)-methyl]-2,2-dimethylpropionamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of C-(3-chloropyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine (231.4 mg, 0.6672 mmol), DMAP (4 mg, 0.033 mmol), and (iPr)2EtN (174 μL, 129 mg, 1 mmol) in dry CH2Cl2 (5 mL), cooled to 0° C., pivaloyl chloride (90 μL, 89 mg, 0.734 mmol) was added under N2 atmosphere, the cooling bath was removed, and the reaction mixture was allowed to stir at ambient temperature for 16 h. The reaction was quenched with H2O and extracted with CH2Cl2 (3×20 mL). The combined CH2Cl2 layers were washed with (1×30 mL each) 0.25M citric acid (pH 2-3), H2O, NaHCO3 sat. aq. sol., and brine, dried over anhydrous MgSO4, and filtered. Sample was purified by filtration through a plug of silica gel, eluting with EtOAc:CH2Cl2 10:1→5:1 (300 mL). Filtrate was concentrated in vacuo, yielding the title compound, as a yellow solid, containing approximately 10% of bis-acetylated material; 1H NMR (CDCl3, 400 MHz) δ 1.23 (s, 9H), 6.75 (d, J=7.6 Hz, 1H), 7.43-7.48 (m, 1H), 7.49-7.55 (m, 2H), 7.60 (d, br, J=7.6 Hz, —NH), 7.72-7.77 (m, 1H), 7.81-7.89 (m, 2H), 7.90 (s, 1H), 8.07-8.14 (m, 2H), 8.20 (d, J=8.8 Hz, 1H), 8.38 (d, J=2.8 Hz, 1H), 8.59 (d, J=2.0 Hz, 1H); MS (ES+): m/z 430.9/432.9 (100/37) [MH+]; HPLC: tR=3.5 min (OpenLynx, polar—5 min).

Workup

  1. customthe cooling bath was removed
  2. customThe reaction was quenched with H2O
  3. extractionextracted with CH2Cl2 (3×20 mL)
  4. washThe combined CH2Cl2 layers were washed with (1×30 mL each) 0.25M citric acid (pH 2-3), H2O, NaHCO3 sat. aq. sol., and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. filtrationSample was purified by filtration through a plug of silica gel
  8. washeluting with EtOAc:CH2Cl2 10:1→5:1 (300 mL)
  9. concentrationFiltrate was concentrated in vacuo

Sources & evidence

ORD record
ord-5a6610f027fa4010b4a19018696aec70
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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