Potassium Phosphate, Tribasic → (R)-tert-butyl 3-(6-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

HRID 1529300Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529300
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2B1OC(C)(C)C(C)(C)O1.Cl[C:38]1[N:43]=[C:42]([O:44][C@@H:45]2[CH2:50][CH2:49][CH2:48][N:47]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:46]2)[CH:41]=[N:40][CH:39]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=1)(=[O:19])=[O:20])[CH:13]=[C:12]2[C:38]1[N:43]=[C:42]([O:44][C@@H:45]2[CH2:50][CH2:49][CH2:48][N:47]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:46]2)[CH:41]=[N:40][CH:39]=1

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 57502428(R)-tert-butyl 3-(6-chloropyrazin-2-yloxy)piperidine-1-carboxylateHCID 679600185-(2,6-difluorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole

Produkt 1

HCID 67958620(R)-tert-butyl 3-(6-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylateAusbeute 88,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A glass microwave reaction vessel was charged with 5-(2,6-difluorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (2.75 g, 5.40 mmol) and (R)-tert-butyl 3-(6-chloropyrazin-2-yloxy)piperidine-1-carboxylate (1.694 g, 5.40 mmol) in p-dioxane/H2O (4:1, 16 mL) followed by A-Phos (0.191 g, 0.270 mmol) and potassium phosphate (2.92 g, 10.80 mmol). The reaction mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 110° C. for 80 min. The reaction mixture was diluted with water and extracted with DCM. The combined organic layers were dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 10-20% EtOAc in Hexanes) to give (R)-tert-butyl 3-(6-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (3.15 g, 4.77 mmol, 88% yield) as a solid. MS (ESI, pos. ion) m/z: 661 (M+1).

Aufarbeitung

  1. customA glass microwave reaction vessel
  2. extractionextracted with DCM
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 10-20% EtOAc in Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-526372e4c6f448fab9e722f69742623a
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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