Potassium Carbonate → HCID 178455333, Verbindung

HRID 389605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 389605
[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[N:24][C:23]([NH2:26])=[C:22]4[O:27][C:28](Cl)=[CH:29][C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:31][C:32]([F:47])([F:46])[C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:31][C:32]([F:46])([F:47])[C:33]1[CH:34]=[C:35]([C:28]2[O:27][C:22]3=[C:23]([NH2:26])[N:24]=[CH:25][C:20]([C:18]4[CH:17]=[N:16][N:15]([C@H:12]5[CH2:13][CH2:14][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][CH2:11]5)[CH:19]=4)=[C:21]3[CH:29]=2)[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 1562653,5-Bis-trifluoromethylphenylboronic acidHCID 178455334HCID 178455334, Verbindung

Produkt 1

HCID 178455333HCID 178455333, VerbindungAusbeute 92,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (83 mg, 0.18 mmol), 3,5-bis(trifluoromethyl)benzeneboronic acid (71 mg, 0.28 mmol), (1,1′-bis-(diphenylphosphino)ferrocene)palladium dichloride (13.5 mg, 0.0186 mmol), and potassium carbonate (77 mg, 0.56 mmol) in 1,4-dioxane (1.0 mL) and water (0.30 mL) was degassed 3× with argon and heated in a microwave reactor at 100° C. for 1 h. The mixture was partitioned between EtOAc and brine and the aqueous phase was extracted with EtOAc. The combined organic fractions were dried over sodium sulfate and concentrated. Purification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM) afforded 104 mg (90%) of the title compound as a foam. 1H NMR (400 MHz, CDCl3): δ 0.06-0.14 (m, 6H) 0.87-0.98 (m, 9H) 1.49-1.64 (m, 2H) 1.85-2.11 (m, 4H) 2.18-2.33 (m, 2H) 3.69-3.82 (m, 2H), 4.17-4.28 (m, 1H), 5.05 (br. s., 1H) 7.34 (s, 1H) 7.70 (s, 1H) 7.82 (s, 1H) 7.92 (s, 1H) 8.00 (s, 1H) 8.31 (s, 2H); MS (ESI): 624.34 [M+H]+; HPLC tR=2.00 min (TOF: nonpolar—3 min).

Aufarbeitung

  1. customwas degassed 3× with argon
  2. customThe mixture was partitioned between EtOAc and brine
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe combined organic fractions were dried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification of the residue by ISCO chromatography (0 to 5% 7 N NH3/MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-d111da58ca0e49f49745af4974f11769
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08378104B2

Notizen zur Reaktion

Wird geladen…