1,2-Dichloroethane → 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide

HRID 82053

反応式

HRID 82053 の反応式
[CH3:1][N:2]([CH3:11])[C:3]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)=[O:4].[OH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[C:21]([C:42](O)=[O:43])[C:22]3[C:27](/[CH:28]=[CH:29]/[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:26][N:25]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[C:23]=3[N:24]=2)=[CH:15][CH:14]=1.CN1CCOCC1.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>C1COCC1.CN(C)C1C=CN=CC=1.CN(C=O)C>[CH3:1][N:2]([CH3:11])[C:3]([N:5]1[CH2:6][CH2:7][N:8]([C:42]([C:21]2[C:22]3[C:27](/[CH:28]=[CH:29]/[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:26][N:25]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[C:23]=3[N:24]=[C:19]([C:16]3[CH:17]=[CH:18][C:13]([OH:12])=[CH:14][CH:15]=3)[CH:20]=2)=[O:43])[CH2:9][CH2:10]1)=[O:4]

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 712909n,n-Dimethylpiperazine-1-carboxamideHCID 1363594996-(4-hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

生成物 1

HCID 1363595104-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
50 °C

実験手順

0.24 mmol of piperazine-1-carboxylic acid dimethylamide were weighted into a reaction tube and dissolved/suspended in 1 ml THF. 1 ml of a DMF stock solution containing 0.24 mmol of 6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid, 1 mmol N-methyl morpholine, 0.01 mmol 4-dimethylaminopyridine, and 0.3 mmol 1-hydroxybenzotriazole were added, followed by 0.3 mmol EDC. The tube was closed and shaken at 50° C. overnight. The THF was left to evaporate, 0.1 ml TFA was added, the volume was adjusted to 2 ml with DMF. The solution was filtered and submitted to prep. RP HPLC purification to give 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide. In order to transform the trifluoro acetic acid salt into a hydrochloric acid salt and—for other examples to cleave acid labile protecting groups—the product obtained above was shaken with 3 ml methanol and 0.5 ml 4M HCl in dioxane at 65° C. for 30 minutes. Then 10 ml diethyl ether was slowly added to the cooled solution, and the formed precipitate was filtered off, washed with 1 ml diethyl ether, and dried in vacuo to afford 0.085 mmol of 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide (35%).

後処理

  1. additionwere added
  2. customThe tube was closed
  3. customto evaporate
  4. addition0.1 ml TFA was added
  5. filtrationThe solution was filtered
  6. customRP HPLC purification

出典と根拠

ORDレコード
ord-68a6c421cfdd40b1a4dd402a6c93c973
出典データセット
uspto-grants-2014_09
特許番号
US08846712B2

関連ノート

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