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

HRID 634254
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 634254
[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]
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Komponenten

6

Edukt 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

Produkt 1

HCID 683281695-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amineAusbeute 17,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6422Trifluoroacetic acidLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-ab3a4cf564aa4b9a8c6b0ea4206ade4f
Quelldatensatz
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09321756B2

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