Carbonate Ion → HCID 178466534, compound

HRID 131251Notes

Reaction equation

HRID 131251 reaction equation
Cl.[N:2]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([C:13]([OH:15])=O)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.Cl.Cl.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:40]=[CH:41][CH:42]=1)[CH2:24][N:25]1[C:29]2=[N:30][CH:31]=[N:32][C:33]([N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[C:28]2[CH:27]=[N:26]1)[CH3:19].ON1C2C=CC=CC=2N=N1.N=C=N.C(=O)([O-])[O-]>CN(C)C=O.C(N(CC)CC)C.C(Cl)Cl>[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH:40]=[CH:41][CH:42]=1)[CH2:24][N:25]1[C:29]2=[N:30][CH:31]=[N:32][C:33]([N:34]3[CH2:35][CH2:36][N:37]([C:13]([C@H:10]4[CH2:9][CH2:8][C@H:7]([N:2]5[CH2:3][CH2:4][CH2:5][CH2:6]5)[CH2:12][CH2:11]4)=[O:15])[CH2:38][CH2:39]3)=[C:28]2[CH:27]=[N:26]1)[CH3:19]

Participants

9

Reactant 5

HCID 19660Carbonate Ion2×HCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 69298924HCID 69298924, compoundHCID 178479759HCID 178479759, compound

Product 1

HCID 178466534HCID 178466534, compoundYield 71.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To trans-4-(1-pyrrolidinyl)cyclohexanecarboxylate hydrochloride (26 mg; compound obtained in Reference example 87(2)) is added successively methylene chloride (3.5 mL), 1-(3-ethoxybenzyl)-4-piperazin-1-yl-1H-pyrazolo[3,4-d]pyrimidine dihydrochloride (30 mg), 0.5M 1-hydroxybenzotriazole in N,N-dimethylformamide (219 μL), triethylamine (35.6 μL) and N-cyclohexylcarbodiimide-N′-propyloxymethylpolystylene (310.4 mg, PS-Carbodiimide, 0.94 mmol/g, Argonaut Technology) and the mixture is stirred at room temperature for 24 hours by using a parallel synthesizer (Quest 210; Argonaut Technology). To the reaction mixture is added macroporous triethylammoniummethylpolystylene carbonate (120 mg, MP-Carbonate 3.04 mmol/g; Argonaut Technology) and the mixture is stirred at room temperature for 3 hours. The liquid layer is separated from the reaction mixture and the residual resin is washed successively with chloroform and methanol. The liquid layer and the washings are combined and concentrated by centrifugal concentrator. The resultant crude product is purified by HPLC (XTerra PerpMS C18 column; Waters Inc., Solvent; 10 mM ammonium carbonate:methanol=1:1→5:95) to give 1-(3-ethoxybenzyl)-4-[4-[[trans-4-(1-pyrrolidinyl)cyclohexyl]carbonyl]piperazin-1-yl]-1H-pyrazolo[3,4-d]-pyrimidine (27 mg, yield; 71%) as an amorphous powder.

Workup

  1. stirringthe mixture is stirred at room temperature for 3 hours
  2. customThe liquid layer is separated from the reaction mixture
  3. washthe residual resin is washed successively with chloroform and methanol
  4. concentrationconcentrated by centrifugal concentrator
  5. customThe resultant crude product is purified by HPLC (XTerra PerpMS C18 column; Waters Inc., Solvent; 10 mM ammonium carbonate:methanol=1:1→5:95)

Sources & evidence

ORD record
ord-ac73ea5c88da45dea8e1fef64b742569
Source dataset
uspto-grants-2008_06
Patent number
US07384952B2

Reaction notes

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