Sodium Hydroxide → 2-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazole

HRID 634204Notes

Reaction equation

HRID 634204 reaction equation
[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[N:14](S(C3C=CC(C)=CC=3)(=O)=O)[CH:13]=[C:12]4[C:28]3[CH:33]=[N:32][CH:31]=[C:30]([CH:34]4[CH2:36][CH2:35]4)[N:29]=3)=[N:7][N:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>O1CCOCC1>[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[NH:14][CH:13]=[C:12]4[C:28]3[CH:33]=[N:32][CH:31]=[C:30]([CH:34]4[CH2:36][CH2:35]4)[N:29]=3)=[N:7][N:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 683289342-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole

Product 1

HCID 683287932-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazoleYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A yellow solution of 2-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (206.8 mg, 0.416 mmol) and NaOH (3.0 M, aq; 2.0 mL, 6.00 mmol) in dioxane (5.0 mL) was heated at 100° C. for 40 min. The reaction was cooled to RT and partitioned between DCM (50 mL) and H2O (30 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (30 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% (10% MeOH-EtOAc)/Hex) furnished 2-cyclopropyl-5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazole (71.0 mg, 0.207 mmol, 50%) as a yellow solid: MS (ESI, pos. ion) m/z: 344.2 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.03 (1H, br. s.), 9.06 (1H, d, J=1.4 Hz), 8.93 (1H, s), 8.41 (1H, s), 8.38 (1H, s), 7.82 (1H, dd, J=8.5, 1.7 Hz), 7.61 (1H, d, J=8.6 Hz), 2.29-2.38 (1H, m), 2.20-2.29 (1H, m), 1.13-1.25 (8H, m).

Workup

  1. custompartitioned between DCM (50 mL) and H2O (30 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with DCM (30 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0-100% (10% MeOH-EtOAc)/Hex)

Sources & evidence

ORD record
ord-27ebbb167c514c4496773c89af93e342
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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