Acetic Acid → HCID 178478158, compound

Participants

Reaction Steps

With gentle heating, 195 mg (0.75 mmol) of 3-amino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine (see Step 1.6) and 135 mg of acetic acid are dissolved in 20 ml of methanol. Then, at RT, 1.0 mmol of tetrazole-5-carbaldehyde is added and the reaction mixture is stirred overnight to complete the reaction, during which a solid separates out. Concentration by evaporation to approximately half volume and filtration yield 4-(3-chloro-phenylamino)-3-[(tetrazol-5-yl)-methyleneamino]-1H-pyrazolo[3,4-d]pyrimidine. More material can be recovered from the mother liquor by concentration by evaporation and stirring the residue in isopropanol. Under a nitrogen atmosphere, 208 mg of the above intermediate are dissolved in 27 ml of DMEU and, with ice cooling, 4.2 ml (4.2 mmol) of DIBAL-H are added and the mixture is stirred for 7 hours. 13 ml of ethyl acetate are added and the mixture is stirred for 30 min and diluted with 130 ml of methanol. 0.9 ml of water and 9 g of Na2SO4 are added to the precipitate, followed by stirring for 30 min and then filtration. The filtrate is concentrated by evaporation (RV, HV) and chromatographed (SiO2; CH2Cl2/−methanol=4:1) and the crude product is stirred in isopropanol/diethyl ether to yield 4-(3-chloro-phenylamino)-3-[(tetrazol-5-yl)-methylamino]-1H-pyrazolo[3,4-d]pyrimidine:HPLC: tRet(grad20-100)=6.7; FAB MS (M+H)+=343.

Provenance & Evidence