Reaktion #168034

Reaktionsgleichung

4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde

2-fluoroethanol

NaH

→

2-(3,5-dimethyl-1H-indazol-4-yl)-4-(2-fluoroethoxy)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigereaction complete
2. 2
   EinengenThe reaction mixture was concentrated
3. 3
   Sonstigethe residue was partitioned between saturated aqueous NH4Cl solution and DCM
4. 4
   SonstigeThe layers were separated
5. 5
   Extraktionthe aqueous layer was extracted further with DCM
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe residue was purified by FCC (0-100% EtOAc/heptane)

Vorschrift

To a solution of 4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde (30 mg, 0.063 mmol) in THF (3 mL) was added 2-fluoroethanol (16.2 mg, 0.25 mmol) and NaH (15.1 mg, 0.63 mmol, 60% in mineral oil). The mixture was stirred at room temperature for 4 h. LC-MS showed reaction complete. The reaction mixture was concentrated and the residue was partitioned between saturated aqueous NH4Cl solution and DCM. The layers were separated and the aqueous layer was extracted further with DCM. The organics were combined and concentrated. The residue was purified by FCC (0-100% EtOAc/heptane) to provide 2-(3,5-dimethyl-1H-indazol-4-yl)-4-(2-fluoroethoxy)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.47 (d, J=8.59 Hz, 1H), 7.34 (s, 1H), 7.15 (d, J=7.71 Hz, 1H), 7.06 (d, J=1.39 Hz, 1H), 6.92 (dd, J=1.52, 7.71 Hz, 1H), 4.71-4.81 (m, 2H), 4.67 (s, 2H), 4.13 (s, 2H), 3.33-3.39 (m, 2H), 3.05 (t, J=5.56 Hz, 2H), 2.88 (td, J=6.93, 13.80 Hz, 1H), 2.32 (s, 3H), 2.27 (s, 3H), 1.98 (s, 3H), 1.25 (d, J=6.82 Hz, 6H); MS (ESE) m/z 474.4 (M+H)+.

Quelle