Trifluoroacetic acid → tert-butyl ((6-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

HRID 1520534Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1520534
Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[S:8][C:5]2=[N:6][CH:7]=1.[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@H:26]([OH:37])[C:27]1[CH:32]=[CH:31][C:30]([Sn](C)(C)C)=[CH:29][CH:28]=1)=[O:23].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(NC(=O)[O-])(C)(C)C.FC(F)(F)C(O)=O>CN(C)C=O.O.C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@@H:26]([C:27]1[CH:28]=[CH:29][C:30]([C:2]2[CH:3]=[C:4]3[N:10]=[C:9]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[S:8][C:5]3=[N:6][CH:7]=2)=[CH:31][CH:32]=1)[OH:37])=[O:23]

Komponenten

10

Edukt 5

HCID 6422Trifluoroacetic acidHCID 521585Tris(furan-2-yl)phosphaneHCID 21252905Tert-butylcarbamateHCID 866953832,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamideHCID 86695489Tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

Produkt 1

HCID 86695488tert-butyl ((6-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)methyl)carbamateAusbeute 16,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate (156 mg, 0.45 mmol), 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethylstannyl)phenyl)-propan-2-yl)acetamide (200 mg, 0.45 mmol) and tris(2-furyl)phosphine (21 mg, 0.090 mmol) Tris(dibenzylideneacetone)dipalladium(0) (41 mg, 0.045 mmol) in dimethylformamide (2.5 mL) is heated at 65° C. for 3 hours under nitrogen. The mixture is then cooled, diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). Extracts are dried over Na2SO4 and concentrated to get crude title compound. m/z (Cl) M+1 543. To a solution of crude tert-butylcarbamate (200 mg, 0.452 mmol) in DCM (3 mL) is added trifluoroacetic acid (0.5 mL) and stirred at room temperature for 3 hours. Reaction is diluted with toluene (10 mL), concentrated under vacuum, basified with saturated aq NaHCO3 and extracted using ethyl acetate (3×10 mL). Extracts are dried over Na2SO4, concentrated and crude compound adsorbed on celite and purified on silica gel column using 0 to 20% methanol in ethyl acetate to give the title compound (40 mg). 1HNMR (DMSO-d6): 4.17 (m, 2H). 4.27 (m, 1.5H), 4.43 (m, 0.5H), 4.59 (m, 0.5H), 4.70 (m, 0.5H), 4.93 (m, 1H), 6.01 (m, 1H), 6.54 (1H), 7.50 (d, 2H), 7.80 (d, 2H), 8.51 (m, 1H), 8.64 (d, 1H), 8.87 (d, 1H), m/z (Cl) M+H 443.

Aufarbeitung

  1. temperatureThe mixture is then cooled
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. dry with materialExtracts are dried over Na2SO4
  4. concentrationconcentrated
  5. customto get crude title compound
  6. customReaction
  7. concentrationconcentrated under vacuum
  8. extractionextracted
  9. dry with materialExtracts are dried over Na2SO4
  10. concentrationconcentrated
  11. custompurified on silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-44bc91aeae56481685d35ad803acafdc
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073894B2

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