StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Diisopropylethylamine → 5-(3-((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)carbamoyl)-4-methoxyphenyl)-2-(4-fluorophenyl)-N-methyl-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridine-3-carboxamide

HRID 1854760
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1854760
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[O:57][C:35]3=[N:36][C:37]([NH:51][CH2:52][C:53]([F:56])([F:55])[F:54])=[C:38]([C:40]4[CH:41]=[CH:42][C:43]([O:49][CH3:50])=[C:44]([CH:48]=4)[C:45]([OH:47])=O)[CH:39]=[C:34]3[C:33]=2[C:58](=[O:61])[NH:59][CH3:60])=[CH:28][CH:27]=1.C(N(C(C)C)C(C)C)C.Cl.[O:72]1[CH:76]=[N:75][C:74]([C:77]([NH2:80])([CH3:79])[CH3:78])=[N:73]1>CN(C=O)C>[O:72]1[CH:76]=[N:75][C:74]([C:77]([NH:80][C:45]([C:44]2[CH:48]=[C:40]([C:38]3[CH:39]=[C:34]4[C:33]([C:58]([NH:59][CH3:60])=[O:61])=[C:32]([C:29]5[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=5)[O:57][C:35]4=[N:36][C:37]=3[NH:51][CH2:52][C:53]([F:55])([F:54])[F:56])[CH:41]=[CH:42][C:43]=2[O:49][CH3:50])=[O:47])([CH3:79])[CH3:78])=[N:73]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866747552-(1,2,4-Oxadiazol-3-yl)propan-2-amine hydrochlorideHCID 904023155-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid

Produkt 1

HCID 85471417
5-(3-((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)carbamoyl)-4-methoxyphenyl)-2-(4-fluorophenyl)-N-methyl-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (22 mg, 0.058 mmol) was added to stirring solution of 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid (20 mg, 0.039 mmol), N-ethyl-N-isopropylpropan-2-amine (0.020 mL, 0.12 mmol) and 2-(1,2,4-oxadiazol-3-yl)propan-2-amine hydrochloride (10 mg, 0.058 mmol) in DMF (1 mL) at rt. The mixture was allowed to stir at rt for 30 min. The crude reaction mixture was then purified via preparative LC/MS with the following conditions: Column:Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 20-mM ammonium acetate; Gradient: 20-100% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 9.5 mg, and its estimated purity by LCMS analysis was 97%. Two analytical LC/MS injections were used todetermine the final purity. Injection 1 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 1 mL/min. retention time: 3.02 min; M+H: 627. Injection 2 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 methanol:water with 10 mM ammonium acetate; MobilePhase B: 95:5 methanol:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 0.5 mL/min. retention time: 3.85 min; M+H: 627. Proton NMR was acquired in deuterated DMSO. 1H NMR (500 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.65 (s, 1H), 8.39-8.31 (m, 1H), 7.97 (dd, J=8.9, 5.5 Hz, 2H), 7.79-7.73 (m, 1H), 7.60 (s, 1H), 7.54 (dd, J=8.5, 2.1 Hz, 1H), 7.37-7.28 (m, 3H), 6.58-6.53 (m, 1H), 4.22-4.08 (m, 2H), 4.01 (s, 3H), 2.79 (d, J=4.6 Hz, 3H), 1.73 (s, 6H).

Aufarbeitung

  1. customThe crude reaction mixture
  2. customwas then purified via preparative LC/MS with the following conditions
  3. waitGradient: 20-100% B over 20 minutes
  4. customa 5-minute hold
  5. additionFractions containing the desired product
  6. customdried via centrifugal evaporation
  7. custom40° C.
  8. waitGradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes
  9. customa 0.5-minute hold
  10. custom40° C.
  11. waitGradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes
  12. customa 0.5-minute hold

Quellen und Nachweise

ORD-Eintrag
ord-edb820cbfc8047f8bbee78ead5c750d4
Quelldatensatz
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08962651B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion