Reaktionsgleichung
[CH3:1][N:2]([CH2:4][CH:5]1[O:10][CH2:9][CH2:8][NH:7][CH2:6]1)[CH3:3].[NH2:11][C:12]1[CH:19]=[C:18](F)[C:15]([C:16]#[N:17])=[CH:14][N:13]=1.C(N(CC)CC)C>>[NH2:11][C:12]1[CH:19]=[C:18]([N:7]2[CH2:8][CH2:9][O:10][CH:5]([CH2:4][N:2]([CH3:3])[CH3:1])[CH2:6]2)[C:15]([C:16]#[N:17])=[CH:14][N:13]=1Komponenten
Reaktionsbedingungen
- Temperatur
- 60 °C
Versuchsvorschrift
A mixture of racemic 2-dimethylaminomethylmorpholine (670 mg, 4.65 mmol), 6-amino-4-fluoronicotinonitrile (intermediate 21, 637 mg, 4.65 mmol) and triethylamine (2.59 ml, 18.6 mmol) was heated at 60° C. in a septum sealed reaction vessel under argon for 10 h. The reaction mixture was evaporated, partitioned between aq. hydrochloric acid (2 M) and DCM (2×), the aqueous layer basified with aqueous NaHCO3, extracted a further 10× with DCM containing 10% MeOH, the combined DCM layers from the basic extraction, dried over Na2SO4 and evaporated. The residue was applied to a 24 g RediSep® silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 20% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a beige foam. (UPLC-MS 6) tR 0.28; ESI-MS 262.2 [M+H]+.
Aufarbeitung
- customsealed
- customreaction vessel under argon for 10 h
- customThe reaction mixture was evaporated
- custompartitioned between aq. hydrochloric acid (2 M) and DCM (2×)
- extractionextracted a further 10× with DCM containing 10% MeOH
- extractionthe combined DCM layers from the basic extraction
- dry with materialdried over Na2SO4
- customevaporated
- custompurified by normal phase chromatography
- washeluting with a gradient from DCM to 20% MeOH in DCM
- additionProduct containing fractions
- customevaporated
Quellen und Nachweise
- ORD-Eintrag
- ord-abe6c3756c9e4f3ab951daf097a042b3
- Quelldatensatz
- uspto-grants-2016_02
- Patentnummer
- US09266883B2
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