Sodium Chloride → N-((3-chloropyrazin-2-yl)methyl)-3-methyloxetane-3-carboxamide

HRID 245681Notes

Reaction equation

HRID 245681 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[C:9]([Cl:10])=[N:8][CH:7]=[CH:6][N:5]=1.[CH3:11][C:12]1([C:16](O)=[O:17])[CH2:15][O:14][CH2:13]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.[Cl-].[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[Cl:10][C:9]1[C:4]([CH2:3][NH:2][C:16]([C:12]2([CH3:11])[CH2:15][O:14][CH2:13]2)=[O:17])=[N:5][CH:6]=[CH:7][N:8]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 140289973-Methyl-3-oxetanecarboxylic AcidHCID 42614233(3-Chloropyrazin-2-yl)methanamine hydrochloride

Product 1

HCID 86674645N-((3-chloropyrazin-2-yl)methyl)-3-methyloxetane-3-carboxamideYield 55.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 2-aminomethyl-3-chloropyrazine hydrochloride (content 77%; 4.34 mmol, 0.81 g) in dichloromethane (150 ml) were added 3-methyl-3-oxetanecarboxylic acid (4.34 mmol, 0.504 g), triethylamine (9.56 mmol, 1.33 ml), 4-dimethylaminopyridine (0.434 mmol, 0.053 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.69 mmol, 1.67 g). After stirring for 16 hours at room temperature the suspension was filtered over decalite and the decalite was washed with dichloromethane. The combined filtrates were washed with 0.3 N hydrochloric acid (350 mL), 0.03 N hydrochloric acid (350 mL) and sodium hydrogencarbonate (aq). All aqueous layers were twice extracted with dichloromethane. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo to give crude material. Solid sodium chloride was added to all aqueous layers and these were extracted five times with dichloromethane. The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo to give a second crop of crude material. The combined crude products were purified using chromatography (silica gel, ethyl acetate) to yield N-((3-chloropyrazin-2-yl)methyl)-3-methyloxetane-3-carboxamide (0.58 g).

Workup

  1. filtrationwas filtered over decalite
  2. washthe decalite was washed with dichloromethane
  3. washThe combined filtrates were washed with 0.3 N hydrochloric acid (350 mL), 0.03 N hydrochloric acid (350 mL) and sodium hydrogencarbonate (aq)
  4. extractionAll aqueous layers were twice extracted with dichloromethane
  5. dry with materialThe combined organic extracts were dried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. customto give crude material
  8. extractionthese were extracted five times with dichloromethane
  9. dry with materialThe combined organic extracts were dried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. customto give a second crop of crude material
  12. customwere purified

Sources & evidence

ORD record
ord-b3e673b4b4c8406ab31da651357208b9
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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