1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

HRID 19370Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19370
[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH2:15][O:16][CH3:17])[C:11]([OH:13])=O)[C:7](=[O:18])[CH:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH3:44][C:45]1([CH3:57])[O:49][C@H:48]([CH2:50][N:51]2[CH:55]=[CH:54][C:53]([NH2:56])=[N:52]2)[CH2:47][O:46]1>ClCCl>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH2:15][O:16][CH3:17])[C:11]([NH:56][C:53]2[CH:54]=[CH:55][N:51]([CH2:50][C@@H:48]3[CH2:47][O:46][C:45]([CH3:57])([CH3:44])[O:49]3)[N:52]=2)=[O:13])[C:7](=[O:18])[CH:6]=1

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 66895181HCID 66895181, Verbindung

Produkt 1

HCID 67504039(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramideAusbeute 27,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

In a round bottom flask under argon was placed (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methoxy-butyric acid (62 mg, 0.19 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (37 μL, 0.21 mmol) and 1-hydoxybenzotriazole (27 mg, 0.20 mmol) and stirred at 25° C. for 2 h. After this time period, 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 45 mg, 0.23 mmol) was added and stirred for 16 h at 25° C. After this time, the reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL) and a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 50% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (26 mg, 27%) as a colorless oil.

Aufarbeitung

  1. customIn a round bottom flask under argon was placed
  2. stirringstirred for 16 h at 25° C
  3. washwashed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL)
  4. dry with materiala saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 50% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-16de470a679948329107fd95f1fee2fd
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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