1,3-Dibromo-5,5-dimethylhydantoin → Tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate

HRID 1972922Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972922
[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:25]N1C(C)(C)C(=O)N(Br)C1=O.[O-]S([O-])=O.[Na+].[Na+]>C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([Br:25])[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

Komponenten

5

Edukt 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 24437Sodium SulfiteHCID 58529617Tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate

Produkt 1

HCID 58529580Tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylateAusbeute 144,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a cooled (−20° C.) solution tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate (1.00 g, 3.00 mmol) in THF (16 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (429 mg, 1.50 mmol) in 3 portions over 10 min. The mixture was allowed warm to 0° C. and stirred for 2 h. The mixture was then stirred at rt for 64 h. Saturated, aqueous Na2SO3 (50 mL) was added and the mixture was warmed to rt. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4) and evaporated. The crude mixture was purified via ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 892 mg (72%) of the desired product. ES-MS m/z 412.26 [M+H]+, HPLC RT (min) 2.62.

Aufarbeitung

  1. stirringThe mixture was then stirred at rt for 64 h
  2. temperaturethe mixture was warmed to rt
  3. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe crude mixture was purified via ISCO® chromatography

Quellen und Nachweise

ORD-Eintrag
ord-957d6071febd4cc0924ff84e43aaa9aa
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431695B2

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