Carbonate Ion → HCID 178466534、化合物

HRID 131251ノート

反応式

HRID 131251 の反応式
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]

参加物

9

反応物 5

HCID 19660Carbonate Ion2 回HCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 69298924HCID 69298924、化合物HCID 178479759HCID 178479759、化合物

生成物 1

HCID 178466534HCID 178466534、化合物収率 71.5%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ac73ea5c88da45dea8e1fef64b742569
出典データセット
uspto-grants-2008_06
特許番号
US07384952B2

反応ノート

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