Réaction #45413

Équation de réaction

3-butyn-1-ol

suspension

N-[4-(4-amino-7-iodothieno [3,2-c]pyridin-3-yl)phenyl]-N′-(3-methylphenyl)urea

→

desired product

Rendement 82.4%

N-{4-[4-amino-7-(4-hydroxy-1-butynyl)thieno[3,2-c]pyridin-3-yl]phenyl}-N′-(3-methylphenyl)urea

Rendement 82.4%

Solvants

piperidine

Conditions de réaction

Traitement

1. 1
   Autreby bubbling nitrogen through the suspension for 5 minutes
2. 2
   TempératureThe resulting homogeneous solution was cooled to room temperature
3. 3
   Concentrationconcentrated under a stream of nitrogen
4. 4
   AutreThe residue was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane

Mode opératoire

A suspension of Example 144A (0.227 g, 0.45 mmol) in piperidine (3 mL) was degassed by bubbling nitrogen through the suspension for 5 minutes, treated with 3-butyn-1-ol (0.069 mL, 0.91 mmol), Pd(PPh3)4 (26 mg, 0.023 mmol), and CuI (5 mg, 0.023 mmol), then heated to 80° C. in a sealed tube for 30 minutes. The resulting homogeneous solution was cooled to room temperature and concentrated under a stream of nitrogen. The residue was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane to provide 164 mg (81%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.29 (s, 3H), 2.65 (t, J=6.78 Hz, 2H), 3.63 (q, J=6.73 Hz, 2H), 4.92 (t, J=5.59 Hz, 1H), 5.70 (s, 2H), 6.81 (d, J=7.46 Hz, 1H), 7.17 (t, J=7.80 Hz, 1H), 7.25-7.28 (m, 1H), 7.32 (s, 1H), 7.37 (d, J=8.48 Hz, 2H), 7.49 (s, 1H), 7.60 (d, J=8.48 Hz, 2H), 7.93 (s, 1H), 8.65 (s, 1H), 8.85 (s, 1H); MS (ESI(+)) m/e 443 (M+H)+.

Source