Phosphorus oxychloride → 2-cyclopropyl-5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole
Reaction equation
[CH:1]1([C:4]([NH:6][NH:7][C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3[I:29])=[O:9])=O)[CH2:3][CH2:2]1.O=P(Cl)(Cl)Cl>O>[CH:1]1([C:4]2[O:9][C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:20])=[O:21])[CH:14]=[C:13]4[I:29])=[N:7][N:6]=2)[CH2:2][CH2:3]1Participants
Conditions
- Temperature
- 110 °C
Procedure
In a 50 mL RBF, N′-(cyclopropanecarbonyl)-3-iodo-1-tosyl-1H-indole-5-carbohydrazide (1.13 g, 2.159 mmol) was treated with POCl3 (5 mL, 53.6 mmol), under argon. The flask was fitted with a reflux condenser. The reaction was stirred and heated at 110° C. for 1.25 h. The crude material was treated with water and extracted with EtOAc. The organic layer was washed with brine, dried, filtered and concentrated to 20 mL of solvent. When about 20 mL of solvent remained, a brown solid precipitated and was collected by filtration. The mother liquor was purified with flash chromatography to give 2-cyclopropyl-5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (570 mg, 1.128 mmol, 52.2). MS (ESI, pos. ion) m/z: 506.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.23 (s, 1H), 8.15 (d, J=8.6 Hz, 1H), 7.94-8.03 (m, 3H), 7.85 (s, 1H), 7.43 (d, J=8.0 Hz, 2H), 2.28-2.37 (m, 4H), 1.09-1.21 (m, 4H).
Workup
- customThe flask was fitted with a reflux condenser
- extractionextracted with EtOAc
- washThe organic layer was washed with brine
- customdried
- filtrationfiltered
- concentrationconcentrated to 20 mL of solvent
- customa brown solid precipitated
- filtrationwas collected by filtration
- customThe mother liquor was purified with flash chromatography
Sources & evidence
- ORD record
- ord-79661426be844c06b90a7e99985e30d2
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09321756B2
Reaction notes
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