Phosphorus oxychloride → 5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-N-phenyl-1,3,4-oxadiazol-2-amine

HRID 634190Notes

Reaction equation

HRID 634190 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([NH:21][NH:22][C:23]([NH:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)=O)=[O:20])[CH:17]=4)[NH:12][CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O>>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]5[O:20][C:23]([NH:25][C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)=[N:22][N:21]=5)[CH:17]=4)[NH:12][CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 867251092-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamide

Product 1

HCID 683287265-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-N-phenyl-1,3,4-oxadiazol-2-amineYield 32%

Procedure

A brown solution of 2-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamide (118.5 mg, 0.287 mmol) and phosphorus oxychloride (3.5 mL, 37.56 mmol) was stirred at 100° C. for 13 h. The reaction was cooled to RT, and excess POCl3 was removed in vacuo. The residue was partitioned between EtOAc (80 mL) and saturated aq NaHCO3 (50 mL). The organic layer was separated, washed with brine (30 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 10-100% EtOAc/Hex) furnished 5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-N-phenyl-1,3,4-oxadiazol-2-amine (36.0 mg, 0.091 mmol, 32%) as a tan solid: MS (ESI, pos. ion) m/z: 395.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.01 (1H, br. s.), 10.53 (1H, s), 9.02 (1H, s), 8.91 (1H, s), 8.37 (1H, d, J=2.7 Hz), 8.36 (1H, s), 7.69-7.74 (1H, m), 7.63 (3H, dd, J=8.5, 1.7 Hz), 7.37 (2H, t, J=7.9 Hz), 7.02 (1H, t, J=7.3 Hz), 2.20-2.30 (1H, m), 1.16-1.21 (2H, m), 1.09-1.15 (2H, m).

Workup

  1. customexcess POCl3 was removed in vacuo
  2. customThe residue was partitioned between EtOAc (80 mL) and saturated aq NaHCO3 (50 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customChromatographic purification of the residue (silica gel, 10-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-0d6db6d544f24206a4669399d65d9264
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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