Bromine → HCID 178419518, compound

To a stirred slurry of 2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-ol (8.83 g, 34 mmol) in CH2Cl2 (150 mL) was added added dropwise a solution of bromine (1.804 ml, 35.0 mmol) in CH2Cl2 (50 mL) over 15 min. After 1 h, the reaction mixture was concentrated to give 6-bromo-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-ol, hydrobromide (14.2 g) as brown solid. LCMS of this solid showed presence of unreacted material and two new products, the expecteded monobrominated and dibrominated products. So, this solid resuspended in MeOH/CH2Cl2 (1:1, 100 mL) and a solution of briomine in CH2Cl2 (1.4 mL) was added over 5 min. After 1 h, the reaction mixture was concentrated and the resulting tan solid was used in the next step without purification. To the above crude product was added N,N-diethylaniline (16.23 ml, 102 mmol) and POCl3 (47.5 ml, 510 mmol) and the mixture was stirred at 120° C. for 16 h. Then, cooled, concentrated and the dark residue taken up in EtOAc (250 mL) and stirred with ice-water for 30 min. Aqueous layer separated and organic layer washed with water (2×50 mL). The combine aqueous layers extracted with EtOAc (100 mL) and the combine organic layers washed with brine (50 mL), dried (Na2SO4/C), filtered and concentrated to give dark paste. Purification by flash column chromatography on silica gel column using 5-10% EtOAc/Hex/5% CH2Cl2 (2.5% increment/lit) provided 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (2.003 g, 5.61 mmol, 16.50% yield) as pale yellow solid. 1H NMR (500 MHz, CDCl3) δ: 8.00 (s, 1H), 7.89-7.83 (m, 1H), 7.43-7.36 (m, 2H), 6.94 (s, 1H), 2.78 (s, 3H). LCMS (M+H) calcd for C13H9BrCl2N3: 355.94. found: 358.0.

1. concentrationthe reaction mixture was concentrated

ORD record

ord-83e4299af9b5468e971a195ac76c5217

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633200B2