Methylamine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide

HRID 545992

Reaktionsgleichung

Reaktionsgleichung von HRID 545992
[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)=[O:23])[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]1C(C)=CC=C[C:38]=1C.CN.O1CCCC1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22](=[O:23])[NH:37][CH3:38])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Komponenten

7

Edukt 5

HCID 6329MethylamineHCID 79372,6-LutidineHCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 67189335{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid

Produkt 1

HCID 671904222(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamideAusbeute 28 %

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, a 2.0 M solution of methylamine in tetrahydrofuran (121 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-methylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide (28 mg, 28%) as a white solid: ESI-LRMS m/e calculated for C21H27ClN4O4S [M+] 466.1, found 467.2 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.24 (m, 2H, CH2), 1.43-1.97 (m, 8H, 4×CH2), 2.18-2.29 (m, 1H, CH), 2.78 (d, J=4.9 Hz, 3H, NCH3), 3.27 (s, 3H, SO2CH3), 3.60 (t, J=7.5 Hz, 1H, CH), 4.67 (s, 2H, NCH2), 5.83-5.91 (m, 1H, NH), 6.77 (d, J=2.4 Hz, 1H, Ar), 7.33 (d, J=2.4 Hz, 1H, Ar), 7.49 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.62 (d, Jm=1.7 Hz, 1H, Ar), 8.06 (s, 1H, NH), 8.11 (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-8a37022e97e240f48b629343adc8c8e3
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

Verknüpfte Notizen

Wird geladen…