2,6-Lutidine → N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 546011

Reaktionsgleichung

Reaktionsgleichung von HRID 546011
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.NC1C=CN(C[C:49]([NH2:51])=[O:50])N=1>C(Cl)Cl>[C:49]([CH2:21][N:18]1[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)=[N:17]1)(=[O:50])[NH2:51]

Komponenten

6

Edukt 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 457919692-(3-amino-1H-pyrazol-1-yl)acetamideHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

Produkt 1

HCID 67190535N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (166 μL, 0.33 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, the crude 2-(3-amino-pyrazol-1-yl)-acetamide (0.30 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (38 mg, 28%) as a white solid: ESI-LRMS m/e calcd for C20H25ClN4O4S [M+] 452.13, found 453.2 [M+H+]; 1H NMR (400 MHz, CD3OD) δ ppm 1.11-1.27 (m, 2H, CH2), 1.46-1.92 (m, 8H, 4×CH2), 2.07-2.27 (m, 1H, CH), 3.28 (s, 3H, SO2CH3), 3.85 (dd, J=8.6, 6.4 Hz, 1H, CH), 4.73 (s, 2H, NCH2), 6.55 (d, J=2.4 Hz, 1H, Ar), 7.53 (d, J=2.4 Hz, 1H, Ar), 7.59 (dd, Jo=8.2, Jm=1.5 Hz. 1H, Ar), 7.71 (d, Jm=1.5 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar).

Aufarbeitung

  1. waitAfter 1 h
  2. waitto proceed for 16 h
  3. washThe reaction solution was washed with 1.0 M aqueous hydrochloric acid solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-fdbc33e4b6de43cc8c870b708a422275
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

Verknüpfte Notizen

Wird geladen…