Diisopropylethylamine → (S)-3-[4-(1H-indazol-5-ylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 503944Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 503944
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[C:62]([O:66][C:67]([N:69]1[CH2:73][CH2:72][C@@H:71]([C:74]2[CH:79]=[CH:78][C:77]([SH:80])=[CH:76][CH:75]=2)[CH2:70]1)=[O:68])([CH3:65])([CH3:64])[CH3:63].OS([O-])(=O)=O.[K+].[O-]S([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:62]([O:66][C:67]([N:69]1[CH2:73][CH2:72][C@@H:71]([C:74]2[CH:79]=[CH:78][C:77]([S:80][C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[NH:7][N:6]=[CH:5]4)=[CH:76][CH:75]=2)[CH2:70]1)=[O:68])([CH3:65])([CH3:63])[CH3:64]

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7619295-bromo-1H-indazoleHCID 59428410(S)-3-(4-mercapto-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 86586342KHSO4 Na2SO4

Produkt 1

HCID 66877589(S)-3-[4-(1H-indazol-5-ylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 62,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

5-Bromo-1H-indazole (200.9 mg, 1.02 mmol), Pd2(dba)3 (115.9 mg), Xantphos (145.9 mg) and DIPEA (0.188 mL) were added to a solution of (S)-3-(4-mercapto-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (285 mg, 1.02 mmol) in 1,4-dioxane (4 mL) under argon atmosphere. The reaction mixture was heated at 100° C. for 18 hours, then cooled to 5° C. and a solution of 10% KHSO4/Na2SO4 was added. The mixture was filtered, the filter cake was washed with EtOAc, and the filtrate was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The resulting crude material was purified via flash chromatography (hexane/EtOAc, 7/3) to give 252 mg (62% yield) of (S)-3-[4-(1H-indazol-5-ylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester.

Aufarbeitung

  1. temperaturecooled to 5° C.
  2. filtrationThe mixture was filtered
  3. washthe filter cake was washed with EtOAc
  4. extractionthe filtrate was extracted with EtOAc
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe resulting crude material was purified via flash chromatography (hexane/EtOAc, 7/3)

Quellen und Nachweise

ORD-Eintrag
ord-1814ea894cdd4aeaaffa745ca44204e5
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07776910B2

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