5-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine → 5-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine

HRID 634146Notes

Reaction equation

HRID 634146 reaction equation
[CH2:1]([O:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]4[S:23][C:22]([NH:24]CC5C=CC(OC)=CC=5)=[N:21][N:20]=4)[CH:17]=3)[NH:12][CH:11]=2)[CH:7]=[N:6][CH:5]=1)[CH3:2]>C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4]1[N:9]=[C:8]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]4[S:23][C:22]([NH2:24])=[N:21][N:20]=4)[CH:17]=3)[NH:12][CH:11]=2)[CH:7]=[N:6][CH:5]=1)[CH3:2]

Participants

3

Reactant 1

HCID 683284415-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 683281955-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amineYield 37.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine (68 mg, 0.148 mmol) in TFA (1 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 30 min, then the solvent was removed. The residue was purified with RP-HPLC (10-40% ACN in H2O with 0.1% TFA) and the fractions were combined and MeCN was removed in vacuo. The mixture was treated with sat. NaHCO3 and extracted with CHCl3/iPrOH (4:1). The combined organic layers were dried, filtered and concentrated to give 5-(3-(6-ethoxypyrazin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (18.5 mg, 0.055 mmol, 36.9% for two steps) as a yellow solid. MS (ESI, pos. ion) m/z: 339 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.94 (1H, br. s.), 8.80 (1H, d, J=1.6 Hz), 8.76 (1H, s), 8.37 (1H, d, J=2.5 Hz), 8.00 (1H, s), 7.76 (1H, dd, J=8.5, 1.7 Hz), 7.54 (1H, d, J=8.4 Hz), 7.27 (2H, s), 4.61 (2H, q, J=7.0 Hz), 1.53 (3H, t, J=7.0 Hz).

Workup

  1. customA glass microwave reaction vessel
  2. customthe solvent was removed
  3. customThe residue was purified with RP-HPLC (10-40% ACN in H2O with 0.1% TFA)
  4. customMeCN was removed in vacuo
  5. additionThe mixture was treated with sat. NaHCO3
  6. extractionextracted with CHCl3/iPrOH (4:1)
  7. customThe combined organic layers were dried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-04fd1dbf8f9a4c5591b8de5a74439963
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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