Cyclohexylamine → (3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

HRID 2367297Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2367297
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([OH:19])=O)[CH2:11]2)[CH:3]=1.CCN(C(C)C)C(C)C.[CH:29]1([NH2:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([NH:35][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:19])[CH2:11]2)[CH:3]=1

Komponenten

6

Edukt 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51356007(3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid

Produkt 1

HCID 51357955(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamideAusbeute 108,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a suspension of (3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid (3.05 g, 10.71 mmol) in CH2Cl2 (50 mL) at room temperature was added Hunig's base (2.70 mL, 15.43 mmol, 1.3 equiv) and cyclohexylamine (1.60 mL, 14.2 mmol, 1.2 equiv), and the resulting mixture was chilled in an ice bath. To this stirred solution was added HATU (4.96 g, 13.1 mmol, 1.1 equiv) in one portion, and the resulting suspension was stirred in the ice bath for 30 minutes. LCMS showed conversion complete. The mixture was diluted with CH2Cl2 (50 mL) and filtered through celite. The filtrate was washed water (2×25 mL) and then brine. The organic was dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 50% EtOAc in CHCl3 afforded the title compound (4.26 g) as a foam. LC-MS (ES) m/z=366 [M+H]+.

Aufarbeitung

  1. temperaturethe resulting mixture was chilled in an ice bath
  2. filtrationfiltered through celite
  3. washThe filtrate was washed water (2×25 mL)
  4. dry with materialThe organic was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washelution of 1% EtOAc in CHCl3 to 50% EtOAc in CHCl3

Quellen und Nachweise

ORD-Eintrag
ord-8c5c112157474633a87409aaf890c52b
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697685B2

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