Reaction #168034

Reaction equation

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

Solvents

THF

Conditions

Workup

1. 1
   Otherreaction complete
2. 2
   ConcentrationThe reaction mixture was concentrated
3. 3
   Otherthe residue was partitioned between saturated aqueous NH4Cl solution and DCM
4. 4
   OtherThe layers were separated
5. 5
   Extractionthe aqueous layer was extracted further with DCM
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue was purified by FCC (0-100% EtOAc/heptane)

Procedure

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)+.

Source