N,1-dimethylpyrrolidin-3-amine → HCID 178423457, Verbindung

HRID 77109Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 77109
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]2)=[CH:5][C:4]=1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=2[N:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:52][NH:53][CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1>>[CH3:52][N:53]([CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1)[C:15]([CH:12]1[CH2:11][CH2:10][N:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([C:18]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=4[N:19]=3)[CH:5]=2)[CH2:14][CH2:13]1)=[O:17]

Komponenten

4

Edukt 3

HCID 2758520N,1-dimethylpyrrolidin-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178423459HCID 178423459, Verbindung

Produkt 1

HCID 178423457HCID 178423457, VerbindungAusbeute 37 %

Reaktionsbedingungen

Temperatur
35 °C

Versuchsvorschrift

Method Q—Step a To a mixture of 1-[4-chloro-3-(5-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid hydrochloride (obtained as described in general method 3,4, step e) (0.01 g, 0.25 mmol) in dcm (2 mL), HATU (0.10 g, 0.26 mmol), TEA (0.07 mL, 0.53 mmol) and methyl-(1-methyl-pyrrolidin-3-yl)-amine (0.03 g, 0.31 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature, washed with ammonium chloride solution (2 mL), filtered through a phase separator and organic phase was filtered by SCX column (eluent: first dcm:MeOH/1:1 then NH3 in MeOH (2N)). This work up was done using the Zinsser Speedy (version 6.1.3). The crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1) to obtain 0.04 g of the title compound (37%). 1H-NMR (400 MHz, CD3OD): δ 1.76-1.93 (5H, m), 2.08-2.23 (2H, m), 2.36-2.48 (6H, m), 2.51-3.09 (9H, m), 3.83-3.86 (2H, m), 5.13-5.20 (1H, m), 7.09-7.13 (2H, m), 7.38-7.40 (3H, m), 7.51 (1H, bs); m/z 466 (M+H)+, retention time (method b)=2.30 (10 min run)

Aufarbeitung

  1. additionwere added
  2. temperaturecooled to room temperature
  3. washwashed with ammonium chloride solution (2 mL)
  4. filtrationfiltered through a phase separator and organic phase
  5. filtrationwas filtered by SCX column (eluent
  6. customThe crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1)

Quellen und Nachweise

ORD-Eintrag
ord-d383427c471749b58667f644ea369eb4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835648B2

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