Reaktion #1270150

Reaktionsgleichung

4-bromo-2-chloro-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide

Intermediate 10

4-bromo-2-chloro-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide

6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine

Intermediate 1

6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine

sodium bicarbonate

→

4-bromo-2-chloro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide

Ausbeute 20.0%

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeirradiation for 1 hour at 110° C.
2. 2
   FiltrationThe reaction mixture was filtered through a Celite pad
3. 3
   Waschenwashed with DCM
4. 4
   WaschenThe combined organic layers were washed brine
5. 5
   Trocknendried over anhydrous MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   SonstigeThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Vorschrift

A mixture of 4-bromo-2-chloro-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (Intermediate 10) (0.0740 g, 0.279 mmol), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.145 g, 0.306 mmol), 1N aq. sodium bicarbonate (0.557 ml, 0.557 mmol) and PdCl2(dppf)-CH2Cl2 (0.0230 g, 0.0280 mmol) in dioxane (1.40 ml) was subjected to microwave irradiation for 1 hour at 110° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with DCM. The combined organic layers were washed brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give 4-bromo-2-chloro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.032 g, 20%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.04-2.12 (2H, m), 2.23-2.27 (2H, m), 3.68-3.74 (2H, m), 4.10-4.15 (2H, m), 5.63-5.69 (1H, m), 7.83 (1H, t, J=2.2 Hz), 7.92 (1H, brs), 8.13-8.16 (1H, m), 8.22 (1H, d, J=8.0 Hz), 8.34-8.42 (4H, m), 8.84 (1H, s). m/z=577.9 [M+1]+.

Quelle