Reaktion #1572729

Reaktionsgleichung

N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide

Intermediate 5

N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide

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

→

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

Ausbeute 23.0%

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeirradiation for 1 hour at 110° C
2. 2
   Filtrationfiltered through a Celite pad
3. 3
   Waschenwashed with CH2Cl2
4. 4
   EinengenThe filtrate was concentrated in vacuo
5. 5
   SonstigeThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1)

Vorschrift

A mixture of N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide (0.114 g, 0.290 mmol) (Intermediate 5), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.070 g, 0.263 mmol), 1 N aq. sodium bicarbonate (0.527 ml, 0.527 mmol) and PdCl2(dppf)-CH2Cl2Adduct (22.0 mg, 2.60 μmol) in dioxane (1.5 ml) was subjected to microwave irradiation for 1 hour at 110° C. The reaction mixture was cooled to room temperature, filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1) to give N-(2-chloro-5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzenesulfonamide (0.030 g, 23%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 1.75-1.98 (2H, m), 2.12-2.26 (2H, m), 3.55-3.72 (2H, m), 3.90-4.05 (2H, m), 5.58-5.72 (1H, m), 7.50-7.70 (3H, m), 7.85 (1H, d, J=7.6 Hz), 8.45 (1H, d, J=8.4 Hz), 8.58-8.72 (2H, m), 8.87 (1H, s), 9.04 (1H, br s), 10.55 (1H, s). m/z=498.09 [M+1]+.

Quelle