Diisopropylethylamine → Benzyl 3-((3-chloropyrazin-2-yl)methylcarbamoyl)azetidine-1-carboxylate

HRID 245686Notes

Reaction equation

HRID 245686 reaction equation
C(N(CC)C(C)C)(C)C.Cl[C:11]([CH:13]1[CH2:16][N:15]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:14]1)=[O:12].Cl.[NH2:28][CH2:29][C:30]1[C:35]([Cl:36])=[N:34][CH:33]=[CH:32][N:31]=1>ClCCl>[Cl:36][C:35]1[C:30]([CH2:29][NH:28][C:11]([CH:13]2[CH2:16][N:15]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:14]2)=[O:12])=[N:31][CH:32]=[CH:33][N:34]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochlorideHCID 86674648Benzyl 3-(chlorocarbonyl)azetidine-1-carboxylate

Product 1

HCID 86674649Benzyl 3-((3-chloropyrazin-2-yl)methylcarbamoyl)azetidine-1-carboxylateYield 82.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N-diisopropylethylamine (109 mmol, 18.01 ml) and a solution of benzyl 3-(chlorocarbonyl)azetidine-1-carboxylate (5.53 g) in dichloromethane (32.5 ml) were added to a stirred suspension of 2-aminomethyl-3-chloropyrazine hydrochloride (content 77%; 21.80 mmol, 5.10 g) in dichloromethane (55 ml) at room temperature to give a dark brown solution. After stirring at room temperature for two hours the reaction mixture was quenched with water and filtered over decalite. Layers were separated and to the aqueous layer saturated aqueous sodium hydrogencarbonate solution was added and the layer was extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried (sodium sulfate), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, dichloromethane/methanol gradient 10/0 to 9/1) to give benzyl 3-((3-chloropyrazin-2-yl)methylcarbamoyl)azetidine-1-carboxylate (6.46 g).

Workup

  1. customto give a dark brown solution
  2. customwas quenched with water
  3. filtrationfiltered over decalite
  4. customLayers were separated and to the aqueous layer saturated aqueous sodium hydrogencarbonate solution
  5. additionwas added
  6. extractionthe layer was extracted three times with dichloromethane
  7. washwashed with brine
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol gradient 10/0 to 9/1)

Sources & evidence

ORD record
ord-15c1e5a54cfe40ee9f8acc5238740969
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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