Cyclobutanecarbonyl chloride → N-[(3-chloro-2-pyrazinyl)(2-phenyl-7-quinolinyl)methyl]cyclobutanecarboxamide

HRID 422589Notes

Reaction equation

HRID 422589 reaction equation
N(C(C)C)(C(C)C)CC.[Cl:10][C:11]1[C:12]([CH:17]([NH2:34])[C:18]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25]3)=[CH:20][CH:19]=2)=[N:13][CH:14]=[CH:15][N:16]=1.[CH:35]1([C:39](Cl)=[O:40])[CH2:38][CH2:37][CH2:36]1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:10][C:11]1[C:12]([CH:17]([NH:34][C:39]([CH:35]2[CH2:38][CH2:37][CH2:36]2)=[O:40])[C:18]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25]3)=[CH:20][CH:19]=2)=[N:13][CH:14]=[CH:15][N:16]=1

Participants

6

Reactant 3

HCID 78705Cyclobutanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 51051365(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine

Product 1

HCID 53629482N-[(3-chloro-2-pyrazinyl)(2-phenyl-7-quinolinyl)methyl]cyclobutanecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of NEt(iPr)2 (150 μL, 111 mg, 0.861 mmol), DMAP (5 mg, 0.04 mmol), and C-(3-chloropyrazin-2-yl)-C-(2-phenylquinolin-7-yl)-methylamine (202 mg, 0.583 mmol) in dry CH2Cl2 (5 mL), cooled by ice/water, is added cyclobutanecarbonyl chloride (75 μL, 78 mg, 0.66 mmol), then the cooling bath is removed, and the reaction mixture is stirred at rt for 3 h. Water is added, the layers are separated, and the aqueous layer is extracted with CH2Cl2 (3×15 mL). The combined CH2Cl2 layers are washed with water, saturated NaHCO3 solution, and brine, dried over MgSO4, filtered and concentrated to give crude material as yellow foam, which is used for the next step without purification. 1H NMR (CDCl3, 400 MHz) δ 1.81-1.90 (m, 1H), 1.90-2.02 (m, 1H), 2.11-2.23 (m, 2H), 2.23-2.35 (m, 2H), 3.12 (quint, J=8.4 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 7.43-7.48 (m, 1H), 7.48-7.54 (m, 2H), 7.73 (dd, J=2.0, 8.4 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.90 (d, J=0.8 Hz, 1H), 8.07-8.12 (m, 2H), 8.19 (d, J=8.4 Hz, 1H), 8.38 (d, J=2.4 Hz, 1H), 8.58 (d, J=2.4 Hz, 1H). MS (ES+): m/z 429.0/431.0 (38/13) [MH+], 469.8/471.8 (6/2) [MH++MeCN]. HPLC: tR=3.6 min (MicromassZQ, polar—5 min).

Workup

  1. customthe cooling bath is removed
  2. additionWater is added
  3. customthe layers are separated
  4. extractionthe aqueous layer is extracted with CH2Cl2 (3×15 mL)
  5. washThe combined CH2Cl2 layers are washed with water, saturated NaHCO3 solution, and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude material as yellow foam, which
  10. customis used for the next step without purification
  11. customHPLC: tR=3.6 min (MicromassZQ, polar—5 min)

Sources & evidence

ORD record
ord-d00dd012edaa49b8a6bba8722c2d2c62
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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