HOAt → (1R,6S)-[8-(4,6-Dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]oct-3-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone

HRID 1193139

Reaktionsgleichung

Reaktionsgleichung von HRID 1193139
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[C@@H:16]3[C@@H:11]([CH2:12][CH2:13][NH:14][CH2:15]3)[CH2:10]2)[N:3]=1.[CH3:17][C:18]1[CH:19]=[CH:20][C:21]([C:27]2[N:32]=[CH:31][CH:30]=[CH:29][N:28]=2)=[C:22]([CH:26]=1)[C:23](O)=[O:24].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.CN(C=O)C>[CH3:8][C:6]1[CH:7]=[C:2]([CH3:1])[N:3]=[C:4]([N:9]2[C@@H:16]3[C@@H:11]([CH2:12][CH2:13][N:14]([C:23]([C:22]4[CH:26]=[C:18]([CH3:17])[CH:19]=[CH:20][C:21]=4[C:27]4[N:28]=[CH:29][CH:30]=[CH:31][N:32]=4)=[O:24])[CH2:15]3)[CH2:10]2)[N:5]=1

Komponenten

7

Edukt 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 445172645-Methyl-2-(pyrimidin-2-yl)benzoic acidHCID 68156939(1R,6S)-8-(4,6-Dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]octane

Produkt 1

HCID 52918564(1R,6S)-[8-(4,6-Dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]oct-3-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanoneAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of (1R,6S)-8-(4,6-dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]octane (60 mg, 0.28 mmol), 5-methyl-2-pyrimidin-2-yl-benzoic acid (61.82 mg, 0.29 mmol), HOAT (56.12 mg, 0.41 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (79.1 mg, 0.41 mmol), TEA (83.5 mg, 0.83 mmol) was taken into DMF (5 mL) and stirred at 50° C. for 4 h. The reaction mixture was cooled and diluted with ethyl acetate (50 mL). It was washed with sat. aqueous NaHCO3 solution (2×25 mL) and with water (2×60 mL). The ethyl acetate layer was dried over Na2SO4, filtered and concentrated. The crude product was purified three times on Agilent Basic HPLC system to yield the title compound (24 mg, 21%). MS (ESI) mass calcd. for C24H26N6O, 414.51; m/z found 415.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 9.17-5.47 (m, 7H), 4.89-1.08 (m, 19H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. washIt was washed with sat. aqueous NaHCO3 solution (2×25 mL) and with water (2×60 mL)
  3. dry with materialThe ethyl acetate layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified three times on Agilent Basic HPLC system

Quellen und Nachweise

ORD-Eintrag
ord-7e165ea677d749a38ea25e8a7600b844
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680275B2

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