Trifluoroacetic acid → 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile

HRID 2109714Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2109714
[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[S:14][C:13]([NH:15][CH2:16][C@@H:17]([NH:29]C(=O)OC(C)(C)C)[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:12][CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:29][C@@H:17]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][CH:20]=1)[CH2:16][NH:15][C:13]1[S:14][C:10]([C:5]2[CH:6]=[CH:7][C:8]([F:9])=[C:3]([CH:4]=2)[C:1]#[N:2])=[CH:11][N:12]=1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acid2×HCID 86613766tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Produkt 1

HCID 866137675-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrileAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.18 g, 0.35 mmol) in 7 mL of DCM was added TFA (0.40 mL, 5.2 mmol). After 30 minutes, 2 mL of additional TFA was added. The mixture was stirred for 30 minutes and was then concentrated under reduced pressure. The residue was taken up in 30 mL of 1:1 EtOAc to 2 N aqueous Na2CO3. The mixture was partitioned in a separatory funnel, and the aqueous portion was extracted with 25 mL of EtOAc. The combined organic extracts were washed with brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (2.5% to 10% MeOH/DCM) afforded 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile (0.14 g, 0.33 mmol, 96% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.83 (dd, J=5.8, 2.4 Hz, 1H), 7.76 (ddd, J=8.7, 5.0, 2.4 Hz, 1H), 7.68 (d, J=8.2 Hz, 2H), 7.52 (d, J=7.8 Hz, 2H), 7.48 (s, 1H), 7.35 (t, J=9.0 Hz, 1H), 3.84-3.78 (m, 1H), 3.68-3.63 (m, 1H), 3.55-3.47 (m, 1H), 3.14-3.04 (m, 2H) LCMS (M+H) 421 calc. for C20H19F3N4OS 420.43.

Aufarbeitung

  1. concentrationwas then concentrated under reduced pressure
  2. customThe mixture was partitioned in a separatory funnel
  3. extractionthe aqueous portion was extracted with 25 mL of EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-ed5b5604ca014688967be915648ae71d
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07514566B2

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