1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 3-(3-Chloro-phenyl)-5-[1-(4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethyl]-[1,2,4]oxadiazole

HRID 273156Notes

Reaction equation

HRID 273156 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[S:8][CH:9]=[CH:10][CH:11]=2)=[N:5][N:4]=[C:3]1[S:12][CH:13]([CH3:17])[C:14]([OH:16])=O.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[Cl:41][C:42]1[CH:43]=[C:44]([CH:49]=[CH:50][CH:51]=1)[C:45]([NH:47]O)=[NH:46]>C(OCC)(=O)C.CN(C=O)C>[Cl:41][C:42]1[CH:43]=[C:44]([C:45]2[N:47]=[C:14]([CH:13]([S:12][C:3]3[N:2]([CH3:1])[C:6]([C:7]4[S:8][CH:9]=[CH:10][CH:11]=4)=[N:5][N:4]=3)[CH3:17])[O:16][N:46]=2)[CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 177434532-(4-Methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-propionic acidHCID 178513296HCID 178513296, compound

Product 1

HCID 670708173-(3-Chloro-phenyl)-5-[1-(4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethyl]-[1,2,4]oxadiazole

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

DMF was added to a mixture of 2-(4-Methyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-propionic acid (50 mg, 0.186 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (35.7 mg, 0.186 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (28.5 mg, 0.186 mmol) and 3-chloro-N-hydroxy-benzamidine (29.3 mg, 0.172 mmol) at room temperature and stirred overnight. The reaction mixture was diluted lo with ethyl acetate (75 ml), washed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. DMF (1 ml) was added to the residue and the resulting solution was heated at 135° C. for 3 h to effect cyclization to oxadiazole. After cooling the reaction mixture was diluted with ethyl acetate (75 ml), washed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The title compound (46.5 mg, 66.9%) was purified by SPE chromatography on silica gel using 50 ml 40%, 150 ml 50% ethyl acetate in hexanes. 1H NMR (CDCl3), a (ppm): 8.03 (s, 1H), 7.92 (m, 1H), 7.47 (m, 4H), 7.18 (dd, 1H), 4.99 (q, 1H), 3.64 (s, 3H), 1.97 (d, 3H).

Workup

  1. additionThe reaction mixture was diluted
  2. washwashed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionDMF (1 ml) was added to the residue
  7. temperatureAfter cooling the reaction mixture
  8. additionwas diluted with ethyl acetate (75 ml)
  9. washwashed with water 3 times, once with 1.0 M HCl (30 ml), saturated NaHCO3 (30 ml) and saturated brine (30 ml)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe title compound (46.5 mg, 66.9%) was purified by SPE chromatography on silica gel using 50 ml 40%, 150 ml 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f6c4d0a432654c949921945767f4caa5
Source dataset
uspto-grants-2008_11
Patent number
US07456200B2

Reaction notes

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