Nitrogen → Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

HRID 1854727Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854727
Br[C:2]1[CH:3]=[C:4]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:9][C:5]2=[N:6][C:7]=1[Cl:8].[C:23]([O:27][C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].N#N>O.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[N:6]=[C:5]2[O:9][C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[C:11]([C:12](=[O:13])[NH:14][CH3:15])[C:4]2=[CH:3][C:2]=1[C:34]1[CH:35]=[C:30]([CH:31]=[CH:32][CH:33]=1)[C:28]([O:27][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:29]

Komponenten

8

Edukt 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acidHCID 904024175-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide

Produkt 1

HCID 90402329Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoateAusbeute 88,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of 5-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide (5.0 g, 13 mmol), (3-(tert-butoxycarbonyl)phenyl)boronic acid (2.75 g, 12.4 mmol). Pd(Ph3P)4 (2.26 g, 1.96 mmol) and cesium carbonate (8.49 g, 26.1 mmol) was degassed/charged with N2 and diluted with water (22 ml)/DMF (220 ml). The resultant mixture was then degassed, charged with N2, heated to an internal temperature of 65° C. and allowed to stir under N2 atmosphere for 16 h. The reaction mixture was cooled to rt then diluted with EtOAc and sat. 1M HCl. The layers were separated and the aq layer was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4 filtered and concentrated. The resultant solid was then flashed on SiO2 eluting with a 0-100% EtOAc in hexanes gradient over 16 CV to give tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (5.2 g, 11 mmol, 83% yield) as a slightly yellow solid contaminated with the bis-coupled product di-tert-butyl 3,3′-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridine-5,6-diyl)dibenzoate. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.18 (s, 1H), 8.08-8.02 (m, 2H), 7.95-7.89 (m, 2H), 7.63 (dt, J=7.6, 1.5 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.24-7.18 (m, 2H), 6.03 (d, J=4.3 Hz, 1H), 2.99 (d, J=4.9 Hz, 3H), 1.62 (s, 9H).

Aufarbeitung

  1. customThe resultant mixture was then degassed
  2. additioncharged with N2
  3. temperatureThe reaction mixture was cooled to rt
  4. additionthen diluted with EtOAc and sat. 1M HCl
  5. customThe layers were separated
  6. extractionthe aq layer was extracted with EtOAc (3×10 mL)
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b2c3ea186613495bbbc3c36bf362270f
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962651B2

Notizen zur Reaktion

Wird geladen…