Hydrogen Peroxide → 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-6,8-dioxo-5,7-diazaspiro(3.4)octan-5-yl)-2-fluoro-N-methylbenzamide

HRID 515837Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515837
[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[C:20]([F:28])[CH:19]=3)[C:10]2=S)=[CH:5][C:4]=1[C:30]([F:33])([F:32])[F:31])#[N:2].FC1C=C(N2C(=S)N(C3C=C(C(F)(F)F)C(C#N)=NC=3)C(=O)C32CCC3)C=CC=1[OH:41].C(C1(NC2C=CC(C(NC)=O)=C(F)C=2)CCC1)#N.OO>CO.CCOC(C)=O>[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([NH:24][CH3:25])=[O:23])=[C:20]([F:28])[CH:19]=3)[C:10]2=[O:41])=[CH:5][C:4]=1[C:30]([F:33])([F:32])[F:31])#[N:2]

Komponenten

7

Edukt 4

HCID 784Hydrogen PeroxideHCID 24872560ApalutamideHCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamideHCID 533732145-(5-(3-Fluoro-4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile

Produkt 1

HCID 673732124-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-6,8-dioxo-5,7-diazaspiro(3.4)octan-5-yl)-2-fluoro-N-methylbenzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenzamide (synthesized as described for Example 1 using 5-amino-3-(trifluoromethyl)picolinonitrile (Intermediate 1) and of 4-((1-cyanocyclobutyl)amino)-2-fluoro-N-methylbenzamide (Intermediate 21) as starting materials) (90 mg, 0.19 mmol) and H2O2 (30%, 0.72 mL) in MeOH (8 mL) was stirred at room temperature for 5 days. The reaction mixture was diluted with EtOAc (10 mL) and the organic layer was washed with water, brine, and dried over magnesium sulfate. The residue obtained was purified by reverse phase HPLC (acetonitrile/water:TFA) to obtain 10 mg of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-6,8-dioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenzamide as a white solid. 1H NMR (500 MHz, CDCl3) δ 9.28 (d, 1H), 8.54 (d, 1H), 8.23 (t, 1H), 7.33 (m, 1H), 7.27 (m, 1H), 6.93 (m, 1H), 3.07 (d, 3H), 2.71 (m, 2H), 2.57 (m, 2H), 2.28 (m, 1H), 1.82 (m, 1H).

Aufarbeitung

  1. washthe organic layer was washed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. customThe residue obtained
  4. customwas purified by reverse phase HPLC (acetonitrile/water:TFA)

Quellen und Nachweise

ORD-Eintrag
ord-0bad1f1dea204ca5aab36efa522e31fe
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108944B2

Notizen zur Reaktion

Wird geladen…