Sodium Hydroxide → 3-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-5-amine

HRID 634277Notes

Reaction equation

[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[N:24]=[C:23]([NH2:25])[O:22][N:21]=4)[CH:18]=3)[N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[OH-].[Na+]>O1CCOCC1>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[N:24]=[C:23]([NH2:25])[O:22][N:21]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-oxadiazol-5-amine (220 mg, 0.44 mmol) in 1,4-dioxane (2.2 mL) was added 10% aq NaOH (1.1 mL) and the reaction was heated at 100° C. for 2 h. The mixture was cooled to RT and treated with ice cold water (2.2 mL). The precipitate was collected through filtration and the crude product was purified with preparative HPLC (eluent: 20-100% MeCN in water with 0.01% TFA) to give 3-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-5-amine (25 mg, 17%). MS (ESI, pos. ion) m/z: 336.1 (M+1); 1H NMR (400 MHz, DMSO-d6): δ 11.75 (s, 1H), 9.10 (s, 1H), 8.16 (s, 1H), 7.75-7.64 (m, 4H), 7.52 (d, J=8.4 Hz, 1H), 7.41 (d, J=7.2 Hz, 1H), 6.51 (d, J=8.4 Hz, 1H), 5.54-5.52 (m, 1H), 1.44 (d, J=6.0 Hz, 6H).

Workup

temperatureThe mixture was cooled to RT
filtrationThe precipitate was collected through filtration
customthe crude product was purified with preparative HPLC (eluent: 20-100% MeCN in water with 0.01% TFA)

Sources & evidence

ORD record: ord-d49dfaa7a50a42fb8a31dca9932f8fe3
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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