Water → HCID 67485507, compound

Temperature

20 °C

A mixture of 5-bromo-2,3-dichloropyridine (4.47 g, 19.7 mmol) and NaOH (867 mg, 21.7 mmol) in DMSO (50 mL) was treated with sufficient H2O to effect dissolution. n-PrSH (1.96 mL, 21.7 mmol) was added, then the reaction was stirred at 20° C. for 4 h. The mixture was poured onto crushed ice (200 g) and then extracted with CH2Cl2 (2×100 mL). The combined CH2Cl2 extracts were washed with H2O (3×100 mL) and brine (3×100 mL), before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (IH) provided 5-bromo-3-chloro-2-propylsulfanylpyridine: m/z (ES+)=268.0 [M+H]+. Step 2: Reaction of this bromopyridine (2.73 g, 10.2 mmol) with (Z)-methyl 3-cyclopentyl-2-iodoacrylate (1.84 g, 6.6 mmol), according to the cross-coupling conditions described in Step 2 of Preparation 9, gave (E)-methyl 2-(5-chloro-6-propylsulfanylpyridin-3-yl)-3-cyclopentylacrylate: m/z (ES+)=340.1 [M+H]+. Step 3: Saponification of this ester (770 mg, 2.3 mmol), using a similar protocol to that described by Step 2 of Preparation 3, furnished the title compound: δH (CDCl3): 1.05 (t, 3H), 1.40-1.85 (m, 10H), 2.45-2.60 (m, 1H), 3.20 (t, 2H), 7.15 (d, 1H), 7.40 (d, 1H), 8.15 (d, 1H).

1. dissolutiondissolution
2. additionThe mixture was poured
3. extractionextracted with CH2Cl2 (2×100 mL)
4. washThe combined CH2Cl2 extracts were washed with H2O (3×100 mL) and brine (3×100 mL)
5. dry with materialbefore being dried (MgSO4)
6. filtrationFiltration, solvent evaporation, and column chromatography (IH)

ORD record

ord-2002ec98e1184b7d90b70a32b31c7261

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262196B2