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 387542노트

반응식

HRID 387542 반응식
[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

참가 물질

3

반응물 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

생성물 1

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

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-50ec26c596d4479b8044411e753d5487
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372842B2

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