3-BROMO-5-CHLOROPYRAZOLO[1,5-A]PYRIMIDINE

Intermediate Example A Preparation of 3-bromo-5-chloro-pyrazolo[1 , 5- a]pyrimidine [Intermediate A]To a stirred solution of 5-Chloro-pyrazolo[1 , 5-a]pyrimidine (46.4 g, 0.3 mol), in glacial acetic acid (700 mL), at room temperature, was added bromine (42 mL, 0.81 mol) dropwise. On completion of addition, the mixture was stirred for 1 hour. The precipitate was filtered off, washed with glacial acetic acid and diethyl ether and dried. The filtrate was retained. The residue was suspended in water (500 mL) and the mixture neutralised with concentrated aqueous ammonia. The crude product was filtered, washed with water, isopropanol and hexane and dried to give 3-bromo-5-chloro-pyrazolo[1 , 5- a]pyrimidine [Intermediate A] (34.6 g, 49percent). The retained filtrate was diluted with ice water, neutralised with concentrated aqueous ammonia and the resulting crude product filtered, washed with isopropanol and hexane and dried to give further 3-bromo-5-chloro-pyrazolo[1 , 5-a]pyrimidine [Intermediate A] (23.6 g, 33percent). To a solution of 5-chloropyrazolo[l, 5-a]pyrimidine (2.30 g, 15.0 mmol) in dichloromethane (100 mL) was added N-bromosuccinimide (2.67 g, 15.0 mmol) and the mixture allowed to stir at ambient temperature for 1 hour. The reaction mixture was poured into water, extracted with dichloromethane, and dried over sodium sulfate. The crude product was purified by column chromatography, eluting with 1percent MeOH/dichloromethane and afforded 1.50 g (45percent) of 3-bromo-5-chloropyrazolo[l, 5-a]pyrimidine as a light yellow solid.Part A. 3-Bromo-5-chloro-Dyrazoloil.5-alDyrimicline Sodium acetate [127-09-3] (24.1 g, 293.9 mmol) was added to a solution of 5-chloro- pyrazolo[l, 5-a]pyrimidine [29274-24-6], (30.1 g, 195.7 mmol) in glacial acetic acid (395 mL) and allowed to stir at ambient temperature until all of the solid had dissolved. An ice bath was then put in place, and the solution chilled to 0°C. Bromine [7726-95-6] (11.0 mL, 214.7 mmol) was added drop by drop into the 0°C buffered acetic acid reaction solution over 35 minutes which gradually became a thick stirred suspension. Upon completion of the bromine addition, the suspension was allowed to stir for a further 15 minutes then was slowly poured into an aqueous (5percent w/v) solution (1 L) of sodium metabisulfite [7681-57-4] stirred in an ice bath. Solid sodium hydroxide [1310-73-2] pellets were added to the stirred suspension, at a rate to maintain an internal temperature of less than 40 °C, until pH of the supernatant was determined to be approximately 8 by pH paper. Precipitated product was isolated by filtration, the filter cake washed with water, and allowed to dry to afford 39.8 g of light yellow powder, mp. 173-174°C. *H NMR (400 MHz, DMSO-ds) δ ppm 7.22 (d, J=7.33 Hz, 1 H) 8.44 (s, 1 H) 9.21 (d, J=7.07 Hz, 1 H). NMR (100 MHz, DMSO-ds) δ ppm 82.84, 109.99, 138.94, 143.76, 145.61, 151.18. LRMS (ESI) m/z 231.8/233.8/235.8 [(M+H)]To a mixture 5-chloropyrazolo[l, 5- a]pyrimidine (30g, 195mmol) in acetonitrile (600 mL) was added N-bromosuccinimide (38.3g, 215mmol). The mixture was stirred at room temperature for 1 hour. Solid product was filtered off and washed with IN NaOH and water. Acetonitrile filtrate and all the washes was concentrated in vacuo and suspended in IN NaOH. The solid product was filtered and washed with water. This product was combined with previous solid and dried overnight to obtain 44.2g 3-bromo-5-chloro- pyrazolo[l, 5-a]pyrimidine. LRMS (ESI) m/z 232/234 [(M+H)]Example 17

3-Bromo-5-chloropyrazolo[1,5-A]pyrimidineshows much similarity to 4H-Pyrazolo[1,5-a]pyrimidin-7-one which is a moiety present in a variety of chemical anti-inflammatory and antischistosomal drugs.

Molecular Weight:232.46
XLogP3:2
Hydrogen Bond Acceptor Count:2
Exact Mass:230.91989
Monoisotopic Mass:230.91989
Topological Polar Surface Area:30.2
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes