Potassium Hydroxide → 5-(3-(6-(cyclopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine

HRID 634138Notes

Reaction equation

[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:20]5[S:24][C:23]([NH2:25])=[N:22][N:21]=5)[CH:18]=4)[N:13](S(C4C=CC(C)=CC=4)(=O)=O)[CH:12]=3)[CH:8]=[N:7][CH:6]=2)[CH2:3][CH2:2]1.[OH-].[K+]>O1CCOCC1>[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:20]5[S:24][C:23]([NH2:25])=[N:22][N:21]=5)[CH:18]=4)[NH:13][CH:12]=3)[CH:8]=[N:7][CH:6]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-(6-(cyclopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (97 mg, 0.193 mmol) in p-dioxane (2 mL) followed by 1 M KOH (0.8 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 15 min, then solvent was removed. The residue was purified with RP-HPLC (5-40% ACN in H2O with 0.1% TFA) to give 5-(3-(6-(cyclopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (12.5 mg, 18.6%) as a solid. MS (ESI, pos. ion) m/z: 350 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.80 (1H, br. s.), 8.97 (1H, s), 8.31 (1H, s), 8.22 (1H, d, J=2.7 Hz), 7.62-7.76 (2H, m), 7.52 (2H, d, J=8.4 Hz), 7.27 (1H, br. s.), 2.83 (1H, dt, J=6.9, 3.2 Hz), 0.88-1.00 (2H, m), 0.49-0.60 (2H, m)

Workup

customA glass microwave reaction vessel
customsolvent was removed
customThe residue was purified with RP-HPLC (5-40% ACN in H2O with 0.1% TFA)

Sources & evidence

ORD record: ord-045f54bcbff84ad78acd500216c26d8f
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

Loading…