Trifluoroacetic acid methylene chloride → (e)-5-Cyclopropyl-4-(piperazin-1-yl)-3-(2-(pyridin-3-yl)vinyl)-1h-pyrazolo[3,4-b]pyridine hydrochloride salt

HRID 387542Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 387542
[CH:1]1([C:4]2[C:5]([N:30]3[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]3)=[C:6]3[C:12](/[CH:13]=[CH:14]/[C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)=[N:11][N:10](CC4C=CC(OC)=CC=4)[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:51]>>[ClH:51].[CH:1]1([C:4]2[C:5]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)=[C:6]3[C:12](/[CH:13]=[CH:14]/[C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)=[N:11][NH:10][C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Komponenten

3

Edukt 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 68764339(E)-tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-3-(2-(pyridin-3-yl)vinyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Produkt 1

HCID 178438026(e)-5-Cyclopropyl-4-(piperazin-1-yl)-3-(2-(pyridin-3-yl)vinyl)-1h-pyrazolo[3,4-b]pyridine hydrochloride saltAusbeute 74 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of (E)-tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-3-(2-(pyridin-3-yl)vinyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (385 mg, 0.68 mmol) in 25% TFA/CH2Cl2 was stirred at room temperature. Then the mixture was concentrated in vacuo, and the residue was evaporated from toluene (3×10 mL). TFA (10 mL) was added to the residue, and the mixture was stirred at 60° C. for 4 hours. The solvent was then removed in vacuo, and the residue was evaporated from toluene (20 mL). The residue was dissolved in CH2Cl2 (2 mL) and 2M HCl in Et2O was added. The mixture was stirred at room temperature for 30 minutes. The resulting solid was filtered and washed with additional Et2O and dried to provide (E)-5-cyclopropyl-4-(piperazin-1-yl)-3-(2-(pyridin-3-yl)vinyl)-1H-pyrazolo[3,4-b]pyridine hydrochloride salt (210 mg, 74% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 9.76 (br s, 2H), 9.24 (s, 1H), 9.00 (d, 1H), 8.80 (d, 1H), 8.30 (s, 1H), 8.07 (dd, 1H), 7.93 (d, 1H), 7.59 (d, 1H), 3.78-3.72 (m, 4H), 3.33-3.26 (m, 4H), 2.17-2.10 (m, 1H), 1.06-1.02 (m, 2H), 0.83-0.79 (m, 2H); LCMS (APCI+) m/z 347.1 (M+H)+, Retention time=2.09 minutes.

Aufarbeitung

  1. concentrationThen the mixture was concentrated in vacuo
  2. customthe residue was evaporated from toluene (3×10 mL)
  3. additionTFA (10 mL) was added to the residue
  4. customThe solvent was then removed in vacuo
  5. customthe residue was evaporated from toluene (20 mL)
  6. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  7. addition2M HCl in Et2O was added
  8. stirringThe mixture was stirred at room temperature for 30 minutes
  9. filtrationThe resulting solid was filtered
  10. washwashed with additional Et2O
  11. customdried

Quellen und Nachweise

ORD-Eintrag
ord-50ec26c596d4479b8044411e753d5487
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372842B2

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