Cesium carbonate → 5-(2,4-Difluorophenoxy)-1-isobutyl-6-(morpholin-2-ylmethoxy)-1H-indazole

HRID 1897475

Reaktionsgleichung

Reaktionsgleichung von HRID 1897475
[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2.C([O-])([O-])=O.[Cs+].[Cs+].C(OC([N:37]1[CH2:42][CH2:41][O:40][CH:39]([CH2:43]Br)[CH2:38]1)=O)(C)(C)C>CC(N(C)C)=O.CCOCC.O>[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH2:43][CH:39]1[O:40][CH2:41][CH2:42][NH:37][CH2:38]1)[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 57418765tert-Butyl 2-(bromomethyl)morpholine-4-carboxylateHCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

Produkt 1

HCID 674102795-(2,4-Difluorophenoxy)-1-isobutyl-6-(morpholin-2-ylmethoxy)-1H-indazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.035 g, 0.11 mmol) in DMA (3.5 mL) was added Cs2CO3 (0.11 g, 0.33 mmol). The mixture stirred at room temperature for 1 hour before the addition of 2-bromomethylmorpholine-4-carboxylic acid tert-butyl ester (0.062 g, 0.22 mmol). The resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was diluted with ether and water and the layers were separated. The aqueous layer was extracted with ether (3×) and the combined organic layers were washed with water and brine, and dried over Na2SO4. The crude mixture was concentrated under reduced pressure and purified by reverse phase HPLC to afford the desired product. MS (APCI+) m/z 418 (M+1) detected; 1H NMR (400 mHz, CD3OD) δ 7.90 (s, 1H), 7.38 (s, 1H), 7.21 (s, 1H), 7.11 (m, 1H), 6.84 (m, 2H), 4.22 (m, 2H), 4.18 (d, 2H), 4.05 (m, 2H), 3.31 (m, 3H), 3.03 (m, 2H), 2.31 (m, 1H), 0.92 (d, 6H)

Aufarbeitung

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with ether (3×)
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe crude mixture was concentrated under reduced pressure
  6. custompurified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-55f5e03fece24384963eb9db92cf3728
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08518983B2

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