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 387542Notes

Reaction equation

HRID 387542 reaction equation
[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

Participants

3

Reactant 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

Product 1

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

Conditions

Temperature
60 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-50ec26c596d4479b8044411e753d5487
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

Loading…