Reaktion #1015408

Reaktionsgleichung

(S)—N-(3-(4-(allyloxy)-3-chlorophenyl)-1-(1-cyanocyclopropylamino)-1-oxopropan-2-yl)-2-(allylthio)-6-methylnicotinamide

2-(allylthio)-6-methylnicotinic acid

→

title compound

(E)-(S)-19-Chloro-9-methyl-5-oxo-17-oxa-12-thia-4,10-diaza-tricyclo[16.2.2.0*6,11*]docosa-1(21),6,8,10,14,18(22),19-heptaene-3-carboxylic acid (1-cyano-cyclopropyl)-amide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewith dry
2. 2
   Sonstigedegassed DCM (50 mL) under argon atmosphere
3. 3
   workup.DISSOLUTIONdissolved
4. 4
   Sonstigein dry
5. 5
   Sonstigedegassed DCM (35 ml) under argon atmosphere at 50° C.
6. 6
   Temperatur(reflux)
7. 7
   workup.ADDITIONAfter the addition
8. 8
   SonstigeThe crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 2/1, 1/1)
9. 9
   Sonstigeto yield a brown solid (4 mg; 6%)

Vorschrift

The title compound was prepared in analogy to example 8 starting from 2-(allylthio)-6-methylnicotinic acid with the exception of the macroccyclisation: in a 10 mL round-bottomed flask, (S)—N-(3-(4-(allyloxy)-3-chlorophenyl)-1-(1-cyanocyclopropylamino)-1-oxopropan-2-yl)-2-(allylthio)-6-methylnicotinamide (50 mg, 97.8 μmol, Eq: 1.00) was combined with dry degassed DCM (50 mL) under argon atmosphere and titanium (IV) isopropoxide (16.7 mg, 17.2 μL, 58.7 μmol, Eq: 0.60) was added. This solution was added dropwise (20 min) to a solution of Grubbs II (24.9 mg, 29.4 μmol, Eq: 0.30) dissolved in dry degassed DCM (35 ml) under argon atmosphere at 50° C. (reflux). After the addition, the reaction mixture was heated to 50° C. and stirred for 3 days under argon atmosphere. The crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 2/1, 1/1) to yield a brown solid (4 mg; 6%). m/z=483.0 [M+H]+.

Quelle