Ethoxalyl chloride → HCID 67323825, compound

HRID 1397472Notes

Reaction equation

HRID 1397472 reaction equation
[OH:1][N:2]=[C:3]([C:5]1[CH:6]=[C:7]([CH:29]=[CH:30][CH:31]=1)[C:8]([NH:10][CH2:11][C:12]1([C:18]2[S:19][CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:22]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[O:9])[NH2:4].Cl[C:33](=O)[C:34]([O:36][CH2:37][CH3:38])=[O:35]>N1C=CC=CC=1>[C:23]1([C:21]2[N:22]=[C:18]([C:12]3([CH2:11][NH:10][C:8]([C:7]4[CH:6]=[C:5]([C:3]5[N:4]=[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[O:1][N:2]=5)[CH:31]=[CH:30][CH:29]=4)=[O:9])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[S:19][CH:20]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 20884Ethoxalyl chlorideHCID 86677600HCID 86677600, compound

Product 1

HCID 67323825HCID 67323825, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

3-(N′-Hydroxycarbamimidoyl)-N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)benzamide (6.8 g, 15.57 mmol) was dissolved in anhydrous pyridine (68 mL) and the reaction mixture was cooled to 0° C. Ethyl chlorooxoacetate (5.2 mL, 46.73 mmol) was added dropwise, and the reaction mixture was heated at 60° C. for 1 h, quenched with 1.5N HCl solution, and diluted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 25-30% EtOAc in petroleum ether) to afford ethyl 3-(3-(((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)phenyl)-1,2,4-oxadiazole-5-carboxylate (6.8 g, yield 87%). 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J=7.9 Hz, 1H), 8.11-8.09 (m, 1H), 7.78-7.76 (m, 1H), 7.61-7.59 (m, 2H), 7.44 (s, 1H), 7.32-7.27 (m, 1H), 7.23-7.21 (m, 3H), 4.62-4.57 (q, J=7.0 Hz, 2H), 3.97-3.94 (m, 2H), 3.81-3.76 (m, 2H), 3.56-3.50 (m, 2H), 2.41-2.37 (m, 2H), 2.19-2.12 (m, 2H), 1.53-1.50 (t, J=7.2 Hz, 3H). MS (ESI) m/z: Calculated for C27H26N4O5S: 518.16. found: 517.1 (M−H)−.

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for 1 h
  2. customquenched with 1.5N HCl solution
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 25-30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-bb0e7bce0d7642b9ad4ed759aeca47b9
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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