Cyclobutanecarbonyl chloride → N-[(3-chloro-2-pyrazinyl)-7-quinolinylmethyl]cyclobutanecarboxamide

HRID 386179Notes

Reaction equation

HRID 386179 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](C4C=CC=CC=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][CH:24]=[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)methanamine2×

Product 1

HCID 57680974N-[(3-chloro-2-pyrazinyl)-7-quinolinylmethyl]cyclobutanecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of NEt(iPr)2 (520 μL, 386 mg, 2.99 mmol), DMAP (12 mg, 0.098 mmol), and C-(3-chloropyrazin-2-yl)-C-quinolin-7-ylmethylamine (compound of Formula IV where Q1=quinolin-7-yl) (608 mg, 1.97 mmol) in dry CH2Cl2 (10 mL), cooled by ice/water, was added cyclobutanecarbonyl chloride (250 μL, 260 mg, 2.19 mmol), then the cooling bath was removed, and the reaction mixture was stirred at ambient temperature for 2.5 h. Water was added, the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined CH2Cl2 layers were washed with dilute HCl (pH 2), water, saturated NaHCO3 solution, and brine and dried over MgSO4. The crude material is chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 1:1 (1-21)→1:3 (22-44)→EtOAc (45-56)], yielding the title compound as an orange foam; 1H NMR (CDCl3, 400 MHz) δ 1.81-1.91 (m, 1H), 1.91-2.03 (m, 1H), 2.11-2.23 (m, 2H), 2.23-2.35 (m, 2H), 3.12 (quint, J=8.6 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 7.39 (dd, J=4.0, 8.0 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.82 (d, J=8.6 Hz, 1H), 7.83 (s, 1H), 8.13 (d, J=8.4 Hz, 1H), 8.37 (d, J=2.2 Hz, 1H), 8.56 (d, J=2.2 Hz, 1H), 8.87 (dd, J=1.6, 4.0 Hz, 1H); MS (ES+): m/z 353.1/355.0 (100/39) [MH+].

Workup

  1. customthe cooling bath was removed
  2. additionWater was added
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×20 mL)
  5. washThe combined CH2Cl2 layers were washed with dilute HCl (pH 2), water, saturated NaHCO3 solution, and brine
  6. dry with materialdried over MgSO4
  7. customThe crude material is chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 1:1 (1-21)→1:3 (22-44)→EtOAc (45-56)]

Sources & evidence

ORD record
ord-f80dfd60f4da4101a499c8e7bd88b82a
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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