Reaktion #424500

Reaktionsgleichung

sodium triacetoxyborohydride

2-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yloxy)-2-methylpropanal

3,3-difluoroazetidine hydrochloride

→

desired product

6-Chloro-4-{5-[2-(3,3-difluoro-azetidin-1-yl)-1,1-dimethyl-ethoxy]-pyridin-2-ylamino}-2-methyl-2H-pyridazin-3-one

Lösungsmittel

NaHCO3

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 18 h
3. 3
   Extraktionextracted with DCM (5×20 mL)
4. 4
   TrocknenThe organic layer was dried (MgSO4)
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeThe resultant residue was purified by chromatography (SiO2-50 g, Hex
7. 7
   workup.WAITAcOEt, 7:3 in 20 min

Vorschrift

To a solution of 2-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yloxy)-2-methylpropanal (665 mg, 2.06 mmol, Eq: 1.00) in DCE (70 ml) was added 3,3-difluoroazetidine hydrochloride (347 mg, 2.68 mmol, Eq: 1.30). The mixture was stirred at RT for 1 h, then sodium triacetoxyborohydride (655 mg, 3.09 mmol, Eq: 1.5) was added and stirring was continued for 18 h. The reaction mixture was diluted with saturated NaHCO3 solution and extracted with DCM (5×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by chromatography (SiO2-50 g, Hex:AcOEt, 7:3 in 20 min, then 50% in 30 min) to afford the desired product (566 mg) as a white powder. (M+H)+=400 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (s, 6 H) 2.79 (br. s., 2 H) 3.70-3.81 (m, 4 H) 3.83 (s, 3 H) 6.87 (dd, J=8.84, 0.51 Hz, 1 H) 7.32 (d, J=8.59 Hz, 1 H) 8.10 (d, J=2.78 Hz, 1 H) 8.22 (s, 1 H) 8.28 (s, 1 H).

Quelle