Acetic Acid → HCID 178509144, compound

To the suspension of 2-bromo-4-(2,4-dichlorophenyl)-1,3-thiazole-5-carboxylic acid (0.512 g, 1.45 mmol) in Methylene chloride (10 mL, 200 mmol) and N,N-Dimethylformamide (0.020 mL, 0.26 mmol) was added Thionyl chloride (1.0 mL, 14 mmol), heated to reflux for 2 hours. The mixture was rotavaped, azeotroped with toluene to give the syrup intermediate. The intermediate was dissolved in dry Methylene chloride (10 mL, 200 mmol). N,N-dimethylaminopyridine (17.3 mg, 0.142 mmol) was added followed by N,N-Diisopropylethylamine (0.62 mL, 3.6 mmol). Cyanamide (69.0 mg, 1.64 mmol) was added and the mixture was stirred at r.t. for 1 hour. The mixture was rotavaped to give a crude residue. To the residue was added Acetic acid (10 mL, 200 mmol), followed by Hydrazine (0.200 mL, 6.37 mmol). The solution was heated to 120° C. for 8 hours. The mixture was cooled to r.t., rotavaped to give an oily residue. The residue was neutralized with saturated aqueous NaHCO3 solution to pH˜8, extracted with 10% MeOH/DCM (3×50 mL). The DCM solution was dried over Na2SO4, filtered and rotavaped to give a crude product. Chromatograph in an 80 g ISOC column using MeOH/DCM (0/100 to 5/95) afforded a solid product (0.144 g, 25.4% yield). LCMS: (FA) ES+392, 394, ES− 390, 392. 1H NMR (400 MHz, d-chloroform & d4-Methanol) δ 7.29-7.39 (m, 2H), 7.19-7.22 (m, 1H).

1. temperatureheated
2. temperatureto reflux for 2 hours
3. customazeotroped with toluene
4. customto give the syrup intermediate
5. customto give a crude residue
6. temperatureThe solution was heated to 120° C. for 8 hours
7. temperatureThe mixture was cooled to r.t.
8. customto give an oily residue
9. extractionextracted with 10% MeOH/DCM (3×50 mL)
10. dry with materialThe DCM solution was dried over Na2SO4
11. filtrationfiltered
12. customto give a crude product

ORD record

ord-967d26d18974445ab190c4bbfedfc3ec

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139589B2