Water → 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

HRID 634225Notes

Reaction equation

HRID 634225 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([OH:13])=O)[CH:9]=2)[N:4]([S:14]([C:17]2[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:3]=1.[F:24][C:25]([F:33])([F:32])[CH2:26][NH:27][C:28]([NH:30][NH2:31])=S.Cl.C(N=C=NCCCN(C)C)C.O>CN(C=O)C>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:13][C:28]([NH:27][CH2:26][C:25]([F:33])([F:32])[F:24])=[N:30][N:31]=3)[CH:9]=2)[N:4]([S:14]([C:17]2[CH:18]=[CH:19][C:20]([CH3:21])=[CH:22][CH:23]=2)(=[O:15])=[O:16])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 337883111-Amino-3-(2,2,2-trifluoroethyl)thioureaHCID 683285993-iodo-1-tosyl-1H-indole-5-carboxylic acid

Product 1

HCID 683282975-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amineYield 7.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-iodo-1-tosyl-1H-indole-5-carboxylic acid (1.996 g, 4.52 mmol), N-(2,2,2-trifluoroethyl)hydrazinecarbothioamide (0.783 g, 4.52 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (2.60 g, 13.57 mmol) (Sigma-Aldrich) in DMF (8.0 mL) was heated at 80° C. for 21.25 h, then at 90° C. for 24 h. The solution was cooled to RT. H2O was added and the solution was extracted with EtOAc (3×75 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to give the crude material. The crude material was purified by flash chromatography (10-60% EtOAc in Hex). The fractions were combined and DCM was added to the residue. A solid was present and was removed by filtration to give 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine (180 mg, 0.320 mmol, 7.08%) as an off white solid. MS (ESI, pos. ion) m/z: 562.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (t, J=6.6 Hz, 1H), 8.21 (s, 1H), 8.10-8.16 (m, 1H), 7.89-7.99 (m, 3H), 7.73 (s, 1H), 7.43 (d, J=8.2 Hz, 2H), 4.06-4.20 (m, 2H), 2.33 (s, 3H).

Workup

  1. extractionthe solution was extracted with EtOAc (3×75 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude material
  7. customThe crude material was purified by flash chromatography (10-60% EtOAc in Hex)
  8. additionDCM was added to the residue
  9. customwas removed by filtration

Sources & evidence

ORD record
ord-c0328521d1ea49a399e3822afdd90535
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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