Diisopropylethylamine → {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester

HRID 1797271

Reaktionsgleichung

Reaktionsgleichung von HRID 1797271
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:14][CH3:15])=[C:7](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)[CH:8]=1)#[N:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=C[CH:28]=[CH:29][C:24]=2N=N1.[CH:38](N(C(C)C)CC)(C)C.[NH2:47][C@@H:48]([CH2:54][N:55]1[CH2:60][CH2:59][CH:58]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[CH2:57][CH2:56]1)[CH2:49][NH:50][C:51](=[O:53])[OH:52]>C(Cl)Cl>[C:29]([O:53][C:51](=[O:52])[NH:50][CH2:49][C@@H:48]([NH:47][C:11](=[O:13])/[CH:10]=[CH:9]/[C:7]1[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=1[O:14][CH3:15])[CH2:54][N:55]1[CH2:56][CH2:57][CH:58]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[CH2:59][CH2:60]1)([CH3:28])([CH3:24])[CH3:38]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11458357(E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acidHCID 86759989{(R)-2-Amino-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid

Produkt 1

HCID 68576228{(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (0.36 g, 1.77 mmol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (1.01 g, 2.65 mmol) and diisopropylethylamine (0.46 ml, 2.65 mmol) in DCM (15 ml) is treated with a solution of {(R)-2-Amino-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid .tert.-butyl ester (0.65 g, 1.77 mmol) in DCM (5 ml). The reaction mixture is stirred at ambient temperature for 30 minutes, then washed with saturated aqueous NaHCO3, water and brine. The DCM phase is dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 2% methanol in DCM) to afford {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester. [MH]+ 553.0.

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3, water and brine
  2. dry with materialThe DCM phase is dried over MgSO4
  3. customevaporated
  4. customThe crude product is purified by flash silica chromatography (elution with 2% methanol in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-a4efb02a2a564838af9b4212ee5e93b8
Quelldatensatz
uspto-grants-2006_04
Patentnummer
US07034042B2

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