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

HRID 634268Notes

Reaction equation

HRID 634268 reaction equation
[CH:1]([NH: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]=[N:7][CH:6]=1)([CH3:3])[CH3:2].[OH-].[Na+]>O1CCOCC1>[CH:1]([NH: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]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 683284033-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 683288603-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-5-amineYield 28.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of tert-butyl (3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (0.49 g, 0.8 mmol) in DCM (10 mL) was added TFA (4 mL) at 0° C. The reaction was stirred for 2 h at RT. The solvent was then removed in vacuo and the residue was triturated with Et2O to give 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (0.23 g, 56.2%). MS (ESI, pos. ion) m/z: 506.1 (M+1). To a solution of 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (0.23 g, 0.45 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: 20-80% AcCN in H2O with 0.1% TFA) to give 3-(3-(6-(isopropylamino)pyrazin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-5-amine (45 mg, 28.3%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H NMR (DMSO-d6, 400 MHz): δ 11.81 (s, 1H), 9.19 (s, 1H), 8.20-8.18 (m, 2H), 7.92 (dd, J=8.4, 1.2 Hz, 1H) 7.86 (brs, 2H), 7.63 (s, 1H), 7.47 (d, J=8.4 Hz, 1H), 4.32-4.29 (m, 1H), 1.29 (d, J=6.4 Hz, 6H).

Workup

  1. customThe reaction was quenched with ice cold H2O
  2. customto give a pale yellow precipitate
  3. filtrationThe precipitate was filtered
  4. washwashed with ice cold H2O
  5. customdried under vacuum
  6. customThe crude product was purified with preparative HPLC (eluent: 20-80% AcCN in H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-4d352ff0521e42e7b7c5f77320e26bc9
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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