* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference:
[1] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 2227 - 2238
2
[ 17303-83-2 ]
[ 222840-73-5 ]
Yield
Reaction Conditions
Operation in experiment
100%
With hydrogenchloride; sodium tetrahydroborate In ethanol
Step 1. Preparation of 3-hydroxymethylthiophene-2-boronic acid (1): To a solution of 2-(dihydroxyboranyl)thiophene-3-carboxaldehyde (prepared from thiophene-3-carboxaldehyde dimethyl acetal by a modified literature procedure, see: Gronowitz, S. et al, (1967) Acta Chem. Scand. 21, 2151) (3.34 g, 0.214 mol) in ethanol (20 mL) at 0° C. under nitrogen was added NaBH4 (0.81 g, 0.21 mol) in portions in 10 min. After stirring for 30 min at 0° C., the mixture was quenched with water and NH4 Cl (sat'd aq.). The pH was adjusted with 1N HCl ~5-6 and the mixture was extracted with ethyl acetate (5*30 mL). Evaporation of the extracts afforded the title compound as a white powdery solid (3.5 g, 100percent): 1 H NMR (400 MHz, Acetone-d6 +1 drop D2 O): δ7.52 (d, 1H), 7.03 (d, 1H), 4.78 (s, 2H). The product was kept under nitrogen at -20° C. to avoid decomposition.
Reference:
[1] Patent: US6034089, 2000, A,
3
[ 17303-83-2 ]
[ 71637-34-8 ]
[ 222840-73-5 ]
Reference:
[1] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 2227 - 2238
3-thiophenecarboxaldehyde dimethyl acetal[ No CAS ]
[ 222840-73-5 ]
Yield
Reaction Conditions
Operation in experiment
100%
With hydrogenchloride; sodium tetrahydroborate In ethanol
35.1 2-(4-Carboxyphenyl)-5-(3-cyclopentyloxy-4-methoxyphenyl)-3-(4,6-dimethylpyrimidin-2-yl)thiomethylthiophene
Step 1. Preparation of 3-hydroxymethylthiophene-2-boronic acid (1): To a solution of 2-(dihydroxyboranyl)thiophene-3-carboxaldehyde (prepared from thiophene-3-carboxaldehyde dimethyl acetal by a modified literature procedure, see: Gronowitz, S. et al, (1967) Acta Chem. Scand. 21, 2151) (3.34 g, 0.214 mol) in ethanol (20 mL) at 0° C. under nitrogen was added NaBH4 (0.81 g, 0.21 mol) in portions in 10 min. After stirring for 30 min at 0° C., the mixture was quenched with water and NH4 Cl (sat'd aq.). The pH was adjusted with 1N HCl ~5-6 and the mixture was extracted with ethyl acetate (5*30 mL). Evaporation of the extracts afforded the title compound as a white powdery solid (3.5 g, 100%): 1 H NMR (400 MHz, Acetone-d6 +1 drop D2 O): δ7.52 (d, 1H), 7.03 (d, 1H), 4.78 (s, 2H). The product was kept under nitrogen at -20° C. to avoid decomposition.