Potassium Carbonate → (2S)-1-{N-[2-[(4-methylpiperazin-1-yl) methyl]hexahydro-2,5-methanopentalen-3a (1H)-yl]glycyl}pyrrolidine-2-carbonitrile

HRID 1015535Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1015535
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]23[CH2:18][CH:14]4[CH2:15][CH:16]([CH2:17]2)[C:12]([NH2:19])([CH2:13]4)[CH2:11]3)[CH2:5][CH2:4]1.Cl[CH2:21][C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]#[N:30])=[O:23].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]23[CH2:18][CH:14]4[CH2:13][C:12]([NH:19][CH2:21][C:22]([N:24]5[CH2:28][CH2:27][CH2:26][C@H:25]5[C:29]#[N:30])=[O:23])([CH2:11]2)[CH:16]([CH2:15]4)[CH2:17]3)[CH2:5][CH2:4]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 11073883(2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrileHCID 673005791-[(4-Methylpiperazin-1-yl) methyl]tricyclo[3.3.1.03,7]nonan-3-amine hydrochloride salt

Produkt 1

HCID 24853118(2S)-1-{N-[2-[(4-methylpiperazin-1-yl) methyl]hexahydro-2,5-methanopentalen-3a (1H)-yl]glycyl}pyrrolidine-2-carbonitrileAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirred solution of the hydrochloride (0.33 g, 0.92 mmol) obtained in Step II, in DMSO (3.7 mL) at room temperature under nitrogen atmosphere (2S)-1-(chloroacetyl)pyrrolidine-2-carbonitrile (0.16 g, 0.92 mmol) and K2CO3 (0.76 g, 5.53 mmol) were added. After stirring the reaction mixture for 3 h, it was diluted with EtOAc and washed with water and brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain (2S)-1-{N-[2-[(4-methylpiperazin-1-yl) methyl]hexahydro-2,5-methanopentalen-3a (1H)-yl]glycyl}pyrrolidine-2-carbonitrile as an off-white solid (0.12 g) in 47% yield. m/z (M+1) 386; 1H NMR (CDCl3+CD3OD) 300 MHz δ 4.78 (d, J=5.7 Hz, 1H), 3.85-3.50 (m, 4H), 3.30-3.10 (m, 5H), 2.85-2.70 (m, 8H), 2.52-2.45 (m, 2H), 2.38-2.20 (m, 4H), 2.10-1.90 (m, 4H), 1.70-1.40 (m, 5H), 1.40-1.27 (m, 1H).

Aufarbeitung

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. customThe crude product was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-3a56fb79db38488983932e70f5906a84
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07985759B2

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