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

HRID 545994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 545994
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22]([OH:24])=O)[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.[N:37]1[C:42](C)=[CH:41]C=[CH:39][C:38]=1C.C(NCC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22](=[O:24])[N:37]([CH2:42][CH3:41])[CH2:38][CH3:39])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Komponenten

6

Edukt 4

HCID 79372,6-LutidineHCID 8021DiethylamineHCID 65578Oxalyl chlorideHCID 67189335{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid

Produkt 1

HCID 671896762(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-diethylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution containing {3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid (prepared in example 3, 100 mg, 0.22 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (121 μL, 0.24 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (28 μL, 0.24 mmol) was added to the solution. After 1 h, diethylamine (25 μL, 0.24 mmol) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with saturated aqueous ammonium chloride solution, the organic phase was 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 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-diethylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide (66 mg, 59%) as a white solid: ESI-LRMS m/e calcd for C24H33ClN4O4S [M+] 508.19, found 509.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.08-1.18 (m, 5H, CH3 and CH2), 1.21 (t, J=7.2 Hz, 3H, CH3), 1.43-1.94 (m, 8H, 4×CH2), 2.18-2.27 (m, 1H, CH), 3.26 (s, 3H, SO2CH3), 3.33 (q, J=7.2 Hz, 2H, CH2), 3.39 (q, J=7.2 Hz, 2H, CH2), 3.54 (t, J=7.6 Hz, 1H, CH), 4.80 (s, 2H, NCH2), 6.71 (d, J=2.4 Hz, 1H, Ar), 7.36 (d, J=2.4 Hz, 1H, Ar), 7.43 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.57 (d, Jm=1.7 Hz, 1H, Ar), 7.93 (s, 1H, NH), 8.06 (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 saturated aqueous ammonium chloride solution
  4. concentrationthe organic phase was concentrated in vacuo
  5. 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-e76cf11c436e4588aff1b4a0e443e4e7
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

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