Water → (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide

HRID 546187Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 546187
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:35])[C@@H:16]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[C:26]([Cl:34])[CH:25]=2)[CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)=[N:10]1)(C)(C)C.O1CCCC1.O>C(O)(=O)C>[Cl:34][C:26]1[CH:25]=[C:24]([C@@H:16]([CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:35])[CH:29]=[CH:28][C:27]=1[S:30]([CH3:33])(=[O:32])=[O:31]

Komponenten

5

Edukt 3

HCID 962WaterHCID 8028TetrahydrofuranHCID 67188652(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide

Produkt 1

HCID 24889503(R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamideAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

In a round bottom flask was placed (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide (85 mg, 0.15 mmol), tetrahydrofuran (2 mL), water (0.5 mL) and acetic acid (2 mL). This solution was then stirred at 25° C. until all starting material is consumed (˜4 hr). The reaction was then diluted with water (10 mL) and transferred to a separatory funnel where it was extracted with ethyl acetate (3×10 mL). The organic layers were combined and then washed with saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide (67 mg, 99%) as a white foam: [α]29589=−11.5° (c=0.13, methylene chloride); ES-HRMS m/e calcd for C20H24N3O5SCl (M+H)+ 454.1198, observed 454.1193; 1H NMR (300 MHz, DMSO-d6) δ 1.51 (m, 1H, CH), 1.78-2.30 (m, 8H, 4×CH2), 3.34 (s, 3H, SO2CH3), 3.67 (q, J=5.4 Hz, 2H, OCH2), 3.96 (m, 1H, ArCHCO), 4.00 (m, 2H, NCH2), 4.84 (t, J=5.4 Hz, 1H, OH), 6.41 (d, J=2.1 Hz, 1H, Ar), 7.55 (d, J=2.1 Hz, 1H, Ar), 7.62 (d, Jo=8.3 Hz, 1H, Ar), 7.73 (s, 1H, Ar), 8.02 (d, Jo=8.3 Hz, 1H, Ar), 10.85 (s, 1H, NH).

Aufarbeitung

  1. customIn a round bottom flask was placed
  2. customis consumed (˜4 hr)
  3. additionThe reaction was then diluted with water (10 mL)
  4. customtransferred to a separatory funnel
  5. extractionwhere it was extracted with ethyl acetate (3×10 mL)
  6. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification on an AnaLogix Intelliflash system (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-b52f1507b9df417db038dcc34158a91d
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

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