Trifluoroacetic acid → N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-phenyl-propan-2-yl]cyclopropanesulfonamide

HRID 1661445Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1661445
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH:28]1([S:31](Cl)(=[O:33])=[O:32])[CH2:30][CH2:29]1.C(O)(C(F)(F)F)=O.C(N(CC)CC)C>N1C=CC=CC=1.O.CC#N>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C@@H:19]([NH:21][S:31]([CH:28]4[CH2:30][CH2:29]4)(=[O:33])=[O:32])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chloride2×HCID 59339817(alphaS,betaR)-beta-{[1-(4-Fluorophenyl)-1H-indazole-5-yl]oxy}-alpha-methylbenzeneethanamine

Produkt 1

HCID 24953162N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-phenyl-propan-2-yl]cyclopropanesulfonamideAusbeute 34,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(1R,2S)-1-[1-(4-Fluorophenyl)indazol-5-yl]oxy-1-phenyl-propan-2-amine (1a, 16 mg, 0.044 mmole) was dissolved in dry pyridine (2 mL) and cooled to 0° C. Cyclopropanesulfonyl chloride (16 μl, 0.056 mmole) was added and the mixture was stirred at room temperature for 45 mm. The progression of the reaction was followed by HPLC (R.P C-18, 20-90% gradient of CH3CN in water, 0.1% TFA). After 45 and 75 mm additional portions of cyclopropanesulfonyl chloride (5 and 6 μl respectively) were added. As the reaction proceeded very slowly, triethylamine (27 μl, 0.2 mmol) was added after a total of 2.5 h of stirring. The stirring was continued at ambient temperature for additional 18.5h and the reaction mixture was then partitioned between ethyl acetate and aqueous hydrochloric acid (1.7M). The organic phase was washed twice with aqueous hydrochloric acid (1.7M), then with water and finally with brine. Evaporation and flash chromatography (SiO2, gradient of 0-50% EtOAc in heptane) and finally lyophilization from dioxane gave the title compound (7 mg, 33%) containing 15 mol % of dioxane.

Aufarbeitung

  1. stirringof stirring
  2. customthe reaction mixture was then partitioned between ethyl acetate and aqueous hydrochloric acid (1.7M)
  3. washThe organic phase was washed twice with aqueous hydrochloric acid (1.7M)
  4. customEvaporation and flash chromatography (SiO2, gradient of 0-50% EtOAc in heptane) and finally lyophilization from dioxane

Quellen und Nachweise

ORD-Eintrag
ord-d1f5f929583d46f88e048bb930617b72
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030340B2

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