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

HRID 454956Notes

Reaction equation

HRID 454956 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]3[NH:15][C:16]4[C:21]([C:13]=3[CH2:12][CH2:11][NH:10]2)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:5][CH:4]=1.Cl[C:23]1[N:28]=[CH:27][N:26]=[C:25]2[NH:29][N:30]=[CH:31][C:24]=12>CS(C)=O.C(N(CC)C(C)C)(C)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[C:14]3[NH:15][C:16]4[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:13]=3[CH2:12][CH2:11][N:10]2[C:23]2[N:28]=[CH:27][N:26]=[C:25]3[NH:29][N:30]=[CH:31][C:24]=23)=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 1989161-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 469293111-(4-methoxyphenyl)-2-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2,3,4,9-tetrahydro-1H-beta-carboline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-acd7fa60c4ea4d24912e6b5deec8149f
Source dataset
uspto-grants-2013_07
Patent number
US08497276B2

Reaction notes

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