Diisopropylethylamine → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isopropyl ester

HRID 448585

Reaktionsgleichung

Reaktionsgleichung von HRID 448585
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].Cl[C:15]1[N:20]=[CH:19][N:18]=[C:17]([N:21]2[C:29]3[C:24](=[CH:25][C:26]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:27][CH:28]=3)[CH2:23][CH2:22]2)[CH:16]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(Cl)Cl>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([NH:13][C:15]2[CH:16]=[C:17]([N:21]3[C:29]4[C:24](=[CH:25][C:26]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:27][CH:28]=4)[CH2:23][CH2:22]3)[N:18]=[CH:19][N:20]=2)[CH2:11][CH2:12]1)=[O:6])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 46941577Propan-2-yl 4-aminopiperidine-1-carboxylateHCID 595665261-(6-Chloropyrimidin-4-yl)-5-(methylsulfonyl)indoline

Produkt 1

HCID 498487854-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isopropyl esterAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 18b (1.1 g, 5.9 mmol), 6a (1.5 g, 4.84 mmol) and diisopropylethylamine (3 mL, 18.1 mmol) in 15 mL of DMF was heated at 80° C. for 17 h and at 90° C. for 24 h. The mixture was diluted with 100 mL of DCM, washed with brine (3×50 mL) and the extracts were dried, filtered and concentrated under vacuum. The residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes) and finally purified on preparative HPLC to afford 0.3 g (14%) of 18-1. tR=5.21 (Method 5). EC50: 611 nM.

Aufarbeitung

  1. washwashed with brine (3×50 mL)
  2. customthe extracts were dried
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography (elution with 50-100% ethyl acetate and 0.1% TEA in hexanes)
  6. customfinally purified on preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-93eb12c28a2d44f993aaf834adfc9f75
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481731B2

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