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

Reaktionsgleichung

Reaktionsgleichung von HRID 82053
[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]

Komponenten

9

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-68a6c421cfdd40b1a4dd402a6c93c973
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846712B2

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