Isovaleric Acid → 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazole

HRID 634218Notes

Reaction equation

HRID 634218 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.[CH3:25][CH:26]([CH2:28][C:29](O)=O)[CH3:27].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O=P(Cl)(Cl)Cl>C1COCC1>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:12][C:29]([CH2:28][CH:26]([CH3:27])[CH3:25])=[N:14][N:13]=3)[CH:9]=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]=1

Participants

7

Reactant 5

HCID 10430Isovaleric AcidHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 683285283-iodo-1-tosyl-1H-indole-5-carbohydrazide

Product 1

HCID 683282302-(3-iodo-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazoleYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 150 mL RBF was weighed 3-iodo-1-tosyl-1H-indole-5-carbohydrazide (1.16 g, 2.55 mmol) followed by THF (20 mL), isovalerianic acid (0.29 mL, 2.55 mmol) (TCI America) and N-ethyl-N-isopropylpropan-2-amine (1.11 mL, 6.37 mmol). To this stirring suspension was added HATU (1.07 g, 2.80 mmol) in one portion and the solution was stirred at RT for 2 h. The mixture was concentrated and treated with POCl3 (10 mL, 107 mmol) under argon. The flask was fitted with a reflux condenser and the reaction was heated to 110° C. for 14 h. The excess POCl3 was removed under reduced pressure and the crude residue was treated with EtOAc and a saturated solution of NaHCO3. It was extracted with EtOAc (50 mL) and washed with brine and dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (0-50% EtOAc in Hex) affording 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-isobutyl-1,3,4-oxadiazole (277 mg, 35%) as a white amorphous solid. MS (ESI, pos. ion) m/z: 522.0 (M+H)1. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.24 (s, 1H), 8.17 (d, J=8.6 Hz, 1H), 8.03 (d, J=8.8 Hz, 1H), 7.97 (m, J=8.2 Hz, 2H), 7.87 (s, 1H), 7.43 (m, J=8.2 Hz, 2H), 2.84 (d, J=7.0 Hz, 2H), 2.33 (s, 3H), 2.15 (dt, J=13.5, 6.8 Hz, 1H), 0.99 (d, J=6.7 Hz, 6H).

Workup

  1. concentrationThe mixture was concentrated
  2. customThe flask was fitted with a reflux condenser
  3. temperaturethe reaction was heated to 110° C. for 14 h
  4. customThe excess POCl3 was removed under reduced pressure
  5. additionthe crude residue was treated with EtOAc
  6. extractionIt was extracted with EtOAc (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 (0-50% EtOAc in Hex)

Sources & evidence

ORD record
ord-03258034e8a54189baa0439283e26b8e
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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