Tetrahydrofuran → N-tert-butyl-5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634228Notes

Reaction equation

HRID 634228 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([NH:13][NH2:14])=[O:12])[CH:9]=2)[N:4]([S:15]([C:18]2[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH:3]=1.C1COCC1.[N:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[C:31]=S.Cl.C(N=C=NCCCN(C)C)C>O>[C:33]([NH:30][C:31]1[O:12][C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([S:15]([C:18]2[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=2)(=[O:16])=[O:17])[CH:3]=[C:2]3[I:1])=[N:13][N:14]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11544tert-Butyl isothiocyanateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 683285283-iodo-1-tosyl-1H-indole-5-carbohydrazide

Product 1

HCID 68328282N-tert-butyl-5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 51.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

3-Iodo-1-tosyl-1H-indole-5-carbohydrazide (625 mg, 1.373 mmol) in a 250 mL RBF was treated with THF (25 mL) and 2-isothiocyanato-2-methylpropane (0.871 mL, 6.86 mmol) (Aldrich). The flask was fitted with a reflux condenser and heated at 60° C. for 2.5 h. The reaction was cooled to RT, the THF was removed in vacuo and replaced with DMF (10.00 mL). The solution was treated with N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (395 mg, 2.059 mmol), fitted with a reflux condenser and heated to 80° C. for 2 h. The mixture was treated with H2O and extracted with EtOAc (2×50 mL), washed with brine and dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (eluting with 0-100% EtOAc in Hex) to give N-tert-butyl-5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (378.7 mg, 0.706 mmol, 51.4) as a white amorphous solid. MS (ESI, pos. ion) m/z: 536.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.19 (s, 1H), 8.12 (d, J=8.8 Hz, 1H), 7.98 (s, 1H), 7.90 (dd, J=8.7, 1.5 Hz, 1H), 7.69 (s, 2H), 7.43 (d, J=8.2 Hz, 2H), 2.33 (s, 3H), 1.37 (s, 9H).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. temperatureThe reaction was cooled to RT
  3. customthe THF was removed in vacuo
  4. customfitted with a reflux condenser
  5. temperatureheated to 80° C. for 2 h
  6. extractionextracted with EtOAc (2×50 mL)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography (eluting with 0-100% EtOAc in Hex)

Sources & evidence

ORD record
ord-a75ef5b1364b4153aaeb46b4f56d214e
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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