Triethylamine → 2-(3-Methoxy-[1,2,4]thiadiazol-5-ylamino)-acetamide

HRID 992242Notes

Reaction equation

HRID 992242 reaction equation
Cl.[NH2:2][CH2:3][C:4]([NH2:6])=[O:5].C(N(CC)CC)C.Cl[C:15]1[S:19][N:18]=[C:17]([O:20][CH3:21])[N:16]=1>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(OCC)(=O)C>[CH3:21][O:20][C:17]1[N:16]=[C:15]([NH:2][CH2:3][C:4]([NH2:6])=[O:5])[S:19][N:18]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 2723639Glycinamide hydrochlorideHCID 147635195-Chloro-3-methoxy-1,2,4-thiadiazole

Product 1

HCID 120523732-(3-Methoxy-[1,2,4]thiadiazol-5-ylamino)-acetamideYield 16%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of glycinamide hydrochloride (0.55 g, 5 mmol) in DMF (10 mL) was added triethylamine (1.7 mL, 12 mmol) and the resulting mixture was stirred for 15 min at room temperature. This was added to a solution of 5-chloro-3-methoxy-[1,2,4]thiadiazole (0.38 g, 2.5 mmol, prepared according to the procedure by Goerdeler, J. et al. in Chem. Ber. 1955, 88, 843) in DMF (15 mL). Then, tetra-butylammonium bromide (50 mg) was added and the resulting suspension was heated at 80-85° C. for 1.5 h. On cooling to room temperature, the reaction mixture was diluted with water and ethyl acetate. The organic layer was collected, washed with brine, sat. Sodium bicarbonate solution, brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification by column chromatography on silica gel using a solvent mixture of dichloromethane and methanol (95/5 and 9/1) afforded 2-(3-methoxy-[1,2,4]thiadiazol-5-ylamino)-acetamide (75 mg, 16%) as a white solid. 1H-NMR (MeOD) δ 4.03 (s, 2H, NCH2), 3.94 (s, 3H, OMe); 13C-NMR (MeOD) δ 182.0, 173.3, 170.0, 56.7 (MeO), 47.9; MS (m/z) 189 (M++1), 172, 144, 87.

Workup

  1. customprepared
  2. temperaturethe resulting suspension was heated at 80-85° C. for 1.5 h
  3. temperatureOn cooling to room temperature
  4. customThe organic layer was collected
  5. washwashed with brine, sat. Sodium bicarbonate solution, brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography on silica gel using
  10. additiona solvent mixture of dichloromethane and methanol (95/5 and 9/1)

Sources & evidence

ORD record
ord-1e401faa793449069b19165d8540c6b3
Source dataset
uspto-grants-2002_10
Patent number
US06468977B1

Reaction notes

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