Diisopropylethylamine → (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate

HRID 408010

Reaktionsgleichung

Reaktionsgleichung von HRID 408010
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:24].C(N(C(C)C)C(C)C)C.[Cl:34][C:35]1[C:36](Cl)=[N:37][CH:38]=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41]>CN(C=O)C.CCOC(C)=O>[Cl:34][C:35]1[C:36]([N:21]2[CH2:22][CH2:23][CH:18]([N:15]3[CH2:16][CH2:17][C@H:13]([NH:12][C:3]4[CH:4]=[CH:5][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=4[F:1])[C:14]3=[O:24])[CH2:19][CH2:20]2)=[N:37][CH:38]=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 2782166Methyl 5,6-DichloronicotinateHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

Produkt 1

HCID 67469943(S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinateAusbeute 47,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 1.0 g, 2.8 mmol) in DMF (30 mL) was added N-ethyl-N-isopropylpropan-2-amine (1.1 g, 8.4 mmol) and methyl 5,6-dichloronicotinate (1.7 g, 8.4 mmol) and the reaction was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (250 mL) and washed with water (100 mL), and brine (50 mL), and the combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc:DCM as eluent to yield a solid, which was further precipitated from using isopropanol to give (S)-methyl 5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinate (0.70 g, 47% yield).

Aufarbeitung

  1. washwashed with water (100 mL), and brine (50 mL)
  2. dry with materialthe combined organic phases were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified on silica using a gradient of 1:9 to 1:4 EtOAc
  6. customDCM as eluent to yield a solid, which
  7. customwas further precipitated

Quellen und Nachweise

ORD-Eintrag
ord-7c08e89d10bb488e89b659b4210609b0
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754226B2

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