Reaktion #794503

Reaktionsgleichung

Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate

trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine

Trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine

intermediate 11

Trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine

sodium t-butoxide

intermediate 37

Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate

→

3-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-6-fluoro-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one

Ausbeute 56.3%

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeDry
2. 2
   Sonstigesparged dioxane (1.5 mL)
3. 3
   workup.ADDITIONwas added
4. 4
   Sonstigethe crude partitioned between 10% saturated ammonium chloride (100 mL) and ethyl acetate (200 mL)
5. 5
   TrocknenThe organic phase was dried with magnesium sulfate
6. 6
   Sonstigeevaporated to dryness under reduced pressure
7. 7
   SonstigeThe crude was purified
8. 8
   Sonstigethen triturated with diethyl ether
9. 9
   FiltrationFiltration

Vorschrift

Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate (intermediate 37, 0.310 g, 1.418 mmol), trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine (intermediate 11, 0.311 g, 1.418 mmol), chloro(2-dicyclohexylphosphino-3,6-dimethoxy-2′-4′-6′-tri-1-1,1′-biphenyl)]2-(2-aminoethyl)phenyl)palladium(ii) (0.085 g, 0.106 mmol), and sodium t-butoxide (0.341 g, 3.55 mmol) were scaled in a microwave vial under argon. Dry, sparged dioxane (1.5 mL) was added and the suspension heated at 50° C. After 20 minutes the vial was opened and the crude partitioned between 10% saturated ammonium chloride (100 mL) and ethyl acetate (200 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was purified using silica chromatography (dichloromethane to ethyl acetate gradient) then triturated with diethyl ether. Filtration gave the desired 3-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-6-fluoro-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.295 g, 0.799 mmol, 56.3% yield) as a free flowing cream colored solid. M+1: 370.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.44-2.59 (m, 2 H) 2.63 (s, 3 H) 3.46-3.56 (m, 2 H) 4.50-4.59 (m, 1 H) 5.31 (quin, J=8.20 Hz, 1 H) 7.03 (dd, J=8.02, 2.54 Hz, 1 H) 7.09 (td, J=7.58, 1.08 Hz, 1 H) 7.30 (td, J=7.73, 1.17 Hz, 1 H) 7.52 (dd, J=8.02, 0.39 Hz, 1 H) 7.60 (dd, J=7.82, 0.78 Hz, 1 H) 7.95 (t, J=2.15 Hz, 1 H).

Quelle