Cesium carbonate → tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetate

HRID 1466606Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1466606
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[C:24]4[N:23]=[CH:22]N=CC=4NN=3)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.[C:27]([O:31][C:32](=[O:35])[CH2:33]Br)([CH3:30])([CH3:29])[CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-]>CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:11]=[N:10][N:9]4[CH:8]=[CH:6][CH:22]=[N:23][C:24]=34)=[O:15])=[CH:11][N:10]([CH2:33][C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:35])[N:9]=2)[CH:7]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 19660Carbonate IonHCID 79177tert-Butyl bromoacetate2×HCID 178490636HCID 178490636, Verbindung

Produkt 1

HCID 66900073tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetateAusbeute 141,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 22728543Water ethylacetateLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

N-(3-(5-chloro-2-methoxyphenyl)-1H-pyrazol-4-yl)pyrazolo pyrimidine-3-carboxamide (2.0 g, 5.4 mmol), t-butyl-bromoacetate (0.88 mL, 6.0 mmol), and cesium carbonate (2.1 g, 6.5 mmol) were combined and stirred at 30° C. overnight. The mixture was warmed to 65° C. at which time additional carbonate and t-butylbromoacetate was added and stirred 8 hrs. The mixture was cooled to ambient temperature and stirred overnight, then partitioned EtOAc/water. The organic phase was separated, washed with brine, dried (Na2SO4), filtered through silica gel, and concentrated to a solid. The solid was washed with 1:1 EtOAc/hexanes to yield 1.85 g (71%) of tert-butyl 2-(3-(5-chloro-2-methoxyphenyl)-4-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-1H-pyrazol-1-yl)acetate as yellow crystals. LCMS (ESI) m+H=483.0. 1H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 8.77 (m, 1H), 8.73 (s, 1H), 8.51 (m, 1H0, 8.38 (s, 1H), 8.02 (s, 1H), 7.58 (s, 1H), 7.31 (m, 1H), 6.97 (m, 2H), 4.85 (s, 2H), 3.83 (s, 3H), 1.49 (s, 9H).

Aufarbeitung

  1. additionwas added
  2. stirringstirred 8 hrs
  3. temperatureThe mixture was cooled to ambient temperature
  4. stirringstirred overnight
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered through silica gel
  9. concentrationconcentrated to a solid
  10. washThe solid was washed with 1:1 EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-015c64253466459985697793754c418d
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US08999998B2

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