Methanol → HCID 86708604, Verbindung

HRID 921723Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921723
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][CH:15]3[CH2:18][O:17][CH2:16]3)[CH2:10][CH2:9]2)=[CH:6][C:5]([C:19]#[N:20])=[CH:4][C:3]=1[NH:21][C:22]1[N:27]=[C:26]([NH:28][CH2:29][CH3:30])[C:25]2=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:24]2[N:23]=1.C1[CH2:40][O:39][CH2:38]C1.CCN(C(C)C)C(C)C.C[OH:51]>CCOC(C)=O>[Cl:1][C:2]1[C:3]([NH:21][C:22]2[N:27]=[C:26]([NH:28][CH2:29][CH3:30])[C:25]3=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:24]3[N:23]=2)=[CH:4][C:5]([C:19]#[N:20])=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH:15]2[CH2:18][O:17][CH2:16]2)[C:38](=[O:51])[O:39][CH3:40])[CH2:10][CH2:9]1

Komponenten

6

Edukt 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 86708603HCID 86708603, Verbindung

Produkt 1

HCID 86708604HCID 86708604, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

2-((2-chloro-5-cyano-3-(4-(oxetan-3-ylamino)piperidin-1-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 363)(20 mg, 0.041 mmol) in MeOH (6 mL)/THF (3 mL) at 0° C. (ice bath) was added DIPEA (21.26 μl, 0.122 mmol) and methyl carbonochloride [(60 μl, 0.775 mmol) total 3× (20 μl, 0.258 mmol) portions]. The reaction stirred at 25° C. for 30 min and the mixture was diluted with EtOAc, washed with sat'd NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 40-80% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford methyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)(oxetan-3-yl)carbamate (5.8 mg).

Aufarbeitung

  1. washwashed with sat'd NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude material was purified via preparative LC/MS with the following conditions
  5. waitGradient: 40-80% B over 20 minutes
  6. customa 5-minute hold
  7. additionFractions containing the desired product
  8. customdried via centrifugal evaporation

Quellen und Nachweise

ORD-Eintrag
ord-83937d68286d4d4891c528b4b2d0044c
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

Notizen zur Reaktion

Wird geladen…