N-Methylisopropylamine → (R/S) tert-butyl 2-(((3-(6-(isopropyl(methyl)amino)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl(methyl)carbamate

HRID 59723

Reaktionsgleichung

Reaktionsgleichung von HRID 59723
[CH3:1][NH:2][CH:3]([CH3:5])[CH3:4].C([Li])CCC.F[C:12]1[N:17]=[CH:16][C:15]([C:18]2[C:22]([CH2:23][N:24]([CH3:36])[CH2:25][CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:21][N:20]([CH:37]3[CH2:42][CH2:41][CH2:40][CH2:39][O:38]3)[N:19]=2)=[CH:14][CH:13]=1>C1COCC1>[CH:3]([N:2]([CH3:1])[C:12]1[N:17]=[CH:16][C:15]([C:18]2[C:22]([CH2:23][N:24]([CH3:36])[CH2:25][CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:21][N:20]([CH:37]3[CH2:42][CH2:41][CH2:40][CH2:39][O:38]3)[N:19]=2)=[CH:14][CH:13]=1)([CH3:5])[CH3:4]

Komponenten

5

Edukt 3

HCID 78485N-MethylisopropylamineHCID 90463358tert-butyl N-[2-([[3-(6-fluoropyridin-3-yl)-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl](methyl)amino)ethyl]-N-methylcarbamateHCID 178418339Butyllithium

Produkt 1

HCID 117613430(R/S) tert-butyl 2-(((3-(6-(isopropyl(methyl)amino)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl(methyl)carbamateAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-30 °C

Versuchsvorschrift

To a solution of methyl(propan-2-yl)amine (150 mg, 2.05 mmol, 4.00 equiv) in anhydrous THF (3 mL) maintained under nitrogen at −30° C. was added dropwise a 2.5M solution of n-butyllithium (1 mL, 5.00 equiv) in hexanes. After stirring for 30 min at −30° C., a solution of tert-butyl N-[2-([[3-(6-fluoropyridin-3-yl)-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl](methyl)amino)ethyl]-N-methylcarbamate (200 mg, 0.45 mmol, 1.00 equiv) in THF (3 mL) was added. The resulting solution was stirred at room temperature for 4 h and then quenched by the addition of water (1 mL). The mixture was extracted with 3×10 mL of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuum. The residue was purified on a silica gel column eluted with 0-3% of methanol in dichloromethane to give 0.18 g (80%) of (R/S) tert-butyl 2-(((3-(6-(isopropyl(methyl)amino)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl(methyl)carbamate as a yellow oil. LCMS (method A, ESI): RT=1.11 min, m/z=501.3 [M+H]+.

Aufarbeitung

  1. stirringThe resulting solution was stirred at room temperature for 4 h
  2. customquenched by the addition of water (1 mL)
  3. extractionThe mixture was extracted with 3×10 mL of dichloromethane
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified on a silica gel column
  7. washeluted with 0-3% of methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-287ae51851074eb38750c2d1751c5d95
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440950B2

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