Diisopropylethylamine → 2-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinate

HRID 715548Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 715548
[OH:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[N:9]=[CH:10][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[N:12][CH:13]=1)([CH3:7])[CH3:6].CCN(C(C)C)C(C)C.[CH3:47][P:48](Cl)([CH3:50])=[O:49]>ClCCl>[CH3:47][P:48]([CH3:50])(=[O:49])[O:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[CH:13]=[N:12][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[CH:10][N:9]=1)([CH3:7])[CH3:6]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 517954Dimethylphosphinic chlorideHCID 712275921-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Produkt 1

HCID 712276992-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinateAusbeute 8,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (60 mg, 0.119 mmol) in dichloromethane (DCM) (1127 μl) was added DIEA (62.3 μl, 0.357 mmol) and dimethylphosphinic chloride (40.1 mg, 0.357 mmol) at RT. The mixture was stirred for 2 hours, concentrated and reconstituted in DMSO/MeOH and filtered. The solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water TFA 30-70%, 50 mL/min, 15 min.). The product was free based with PL-HCO3 resin SPE to yield 2-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinate as a white solid (5.8 mg, 8%). 1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J=1.51 Hz, 1H), 8.60 (d, J=1.26 Hz, 1H), 8.48 (s, 1H), 8.38 (s, 1H), 7.83 (d, J=8.53 Hz, 1H), 4.12-4.21 (m, 2H), 3.94-4.03 (m, 2H), 3.88 (dd, J=23.09, 10.04 Hz, 2H), 3.42 (t, J=4.77 Hz, 2H), 2.00 (d, J=13.30 Hz, 1H), 1.88 (d, J=14.05 Hz, 1H), 1.59-1.78 (m, 3H), 1.30-1.56 (m, 15H), 1.07 (s, 3H). MS (m/z) 581.3 (M+H+).

Aufarbeitung

  1. concentrationconcentrated
  2. filtrationfiltered
  3. customThe solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water TFA 30-70%, 50 mL/min, 15 min.)

Quellen und Nachweise

ORD-Eintrag
ord-349321e13bc2463a9f3f690dcd33d624
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09187464B2

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