1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole → 1-(4-methoxyphenyl)-2-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2,3,4,9-tetrahydro-1H-beta-carboline

To a solution of 1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole from step 1 in dimethylsulfoxide (2.4 ml) and N,N-diisopropylethylamine (175 μl) was added a 0.25 M solution of 4-chloro-1H-pyrazolo[3,4-d]pyrimidine in dimethylsulfoxide (800 μl). The mixture was shaken at room temperature for 24 hours. The mixture was evaporated to dryness and the residue shaken at 50° C. in a mixture of ethyl acetate (3 ml) and water (2 ml) for 30 minutes. The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (2 ml). The combined organic layers were evaporated to dryness and the residue dissolved in dimethylsulfoxide (1.6 ml) at 50° C. then purified by reverse phase chromatography on a preparative LC/UV/MS system using a mass triggered fractionation. Compounds were eluted from the HPLC column (Maccel 120-10-C18 SH 10 μm 20 mmID×50 mm) at 88 ml/min with 5-95acetonitrile/water gradient using 0.1% TFA as modifier to yield 1-(4-methoxyphenyl)-2-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2,3,4,9-tetrahydro-1H-beta-carboline. LCMS m/e 397 (M+1).

1. customThe mixture was evaporated to dryness
2. stirringthe residue shaken at 50° C. in a mixture of ethyl acetate (3 ml) and water (2 ml) for 30 minutes
3. customThe organic layer was separated
4. extractionthe aqueous layer re-extracted with ethyl acetate (2 ml)
5. customThe combined organic layers were evaporated to dryness
6. dissolutionthe residue dissolved in dimethylsulfoxide (1.6 ml) at 50° C.
7. customthen purified by reverse phase chromatography on a preparative LC/UV/MS system
8. washCompounds were eluted from the HPLC column (Maccel 120-10-C18 SH 10 μm 20 mmID×50 mm) at 88 ml/min with 5-95acetonitrile/water gradient

ORD 기록

ord-acd7fa60c4ea4d24912e6b5deec8149f

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08497276B2