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

HRID 634254Notes

Reaction equation

HRID 634254 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[S:24][N:23]=[C:22]([NH:25]CC5C=CC(OC)=CC=5)[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].C(OC1N=C(C2C3C(=CC=C(C4SN=C(N)N=4)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)C=CC=1)(C)C.[OH-].[Na+]>C(O)(C(F)(F)F)=O.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[S:24][N:23]=[C:22]([NH2:25])[N:21]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 683283525-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amineHCID 683284615-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine

Product 1

HCID 683281695-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amineYield 17.5%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.35 g, 0.56 mmol) in TFA (3.5 mL) was heated in a Biotage microwave at 100° C. for 30 min. The reaction was cooled to RT. TFA was removed in vacuo and the residue was washed with Et2O (7 mL) to get the crude product (250 mg), which was used in next step without further purification. MS (ESI, pos. ion) m/z: 506.1 (M+1). To a solution of crude 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (0.25 g, 0.442 mmol) in 1,4-dioxane (2.5 mL) was added 10% aq NaOH (1.3 mL) and the reaction was heated at 100° C. for 2 h. The mixture was treated with ice cold water (10 mL), resulting a white precipitate. The precipitate was filtered and washed with ice cold water (˜10 mL) and dried under vacuum. The solid was purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in H2O with 0.01% TFA) to give 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (30 mg, 17.5%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 11.96 (s, 1H), 9.05 (d, J=1.2 Hz, 1H), 8.25 (d, J=2.8 Hz, 1H), 7.76 (dd, J=8.4, 1.6 Hz, 1H), 7.69-7.65 (m, 2H), 7.64 (d, J=8.4 Hz, 1H), 7.46 (t, J=7.2 Hz, 2H), 6.70 (s, 2H), 6.54 (d, J=8 Hz, 1H), 5.61-5.55 (m, 1H), 1.52 (d, J=5.6 Hz, 6H).

Workup

  1. customTFA was removed in vacuo
  2. washthe residue was washed with Et2O (7 mL)
  3. customto get the crude product (250 mg), which
  4. customwas used in next step without further purification
  5. temperaturethe reaction was heated at 100° C. for 2 h
  6. customresulting a white precipitate
  7. filtrationThe precipitate was filtered
  8. washwashed with ice cold water (˜10 mL)
  9. customdried under vacuum
  10. customThe solid was purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in H2O with 0.01% TFA)

Sources & evidence

ORD record
ord-ab3a4cf564aa4b9a8c6b0ea4206ade4f
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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