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

HRID 634265Notes

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])[S: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])[S: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-thiadiazol-5-amine (0.25 g, 0.49 mmol) in 1,4-dioxane (10 mL) was added 10% aq NaOH (5 mL) and the reaction was heated at 100° C. for 2 h. The reaction was quenched with ice cold H2O to give a pale yellow precipitate. The precipitate was filtered, washed with ice cold H2O and dried under vacuum. The crude product was purified with preparative HPLC (eluent: 30-100% MeCN in H2O with 5 mM NH4OAc) to give 3-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (35 mg, 20.2%). MS (ESI, pos. ion) m/z: 352.3 (M+1); 1H NMR (DMSO-d6, 400 MHz): δ 11.65 (brs, 1H), 8.11 (d, J=2.4 Hz, 1H), 7.91 (dd, J=8.4, 1.6 Hz, 1H) 7.85 (brs, 2H), 7.66 (t, J=8, 1H) 7.46 (d, J=8.8, 1H), 7.39 (d, J=7.6, 1H), 6.50 (d, J=8, 1H), 5.58-5.55 (m, 1H), 1.42 (d, J=6 Hz, 6H).

Workup

customThe reaction was quenched with ice cold H2O
customto give a pale yellow precipitate
filtrationThe precipitate was filtered
washwashed with ice cold H2O
customdried under vacuum
customThe crude product was purified with preparative HPLC (eluent: 30-100% MeCN in H2O with 5 mM NH4OAc)

Sources & evidence

ORD record: ord-fc1e62e13aec4bb786e73b91cf87b845
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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