Trifluoroacetic acid → N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 546096Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 546096
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:15]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:40])[C@@H:22]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[C:31]([Cl:39])[CH:30]=3)[CH2:23][CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[N:16]2)[CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=1)[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:40])[C@@H:22]([C:29]2[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[C:31]([Cl:39])[CH:30]=2)[CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[N:16]1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 67190452HCID 67190452, Verbindung

Produkt 1

HCID 67190250N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideAusbeute 83,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

(3-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-phenyl)-carbamic acid tert-butyl ester (prepared in Example 57, 501 mg, 0.83 mmol) was dissolved in methylene chloride (5 mL) and trifluoroacetic acid (500 μL) was added. The reaction stirred at 25° C. for 3 h. The reaction was concentrated in vacuo to half the reaction volume, diluted with toluene and concentrated in vacuo to dryness. The reaction was dissolved in ethyl acetate (25 mL), washed with a saturated aqueous sodium bicarbonate solution (2×10 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate and concentrated in vacuo to give the desired product, N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (348 mg, 83%) as an off white powder: ESI-LRMS m/e calcd for C25H29ClN4O3S [M+] 500.16, found 501.20 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.21 (m, 2H, CH2), 1.41-1.92 (m, 8H, 4×CH2), 2.14-2.32 (m, 1H, CH), 3.25 (s, 3H, SO2CH3), 3.53-3.68 (m, 1H, CH), 5.02 (s, 2H, NCH2), 6.45-6.55 (m, 1H, Ar), 6.56-0.665 (m, 2H, Ar), 6.68 (s, 1H, Ar), 7.00-7.14 (m, 1 H, Ar), 7.32 (s, 1H, Ar), 7.45 (d, Jo=7.8 Hz. 1H, Ar), 7.60 (s, 1H, Ar), 7.75-8.23 (m, 2H, Ar and NH).

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo to half the reaction volume
  2. additiondiluted with toluene
  3. concentrationconcentrated in vacuo to dryness
  4. dissolutionThe reaction was dissolved in ethyl acetate (25 mL)
  5. washwashed with a saturated aqueous sodium bicarbonate solution (2×10 mL), saturated aqueous brine solution (10 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-0329cd75cdd84679a6a28d1091d42254
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

Notizen zur Reaktion

Wird geladen…