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 387542ノート

反応式

HRID 387542 の反応式
[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

参加物

3

反応物 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

生成物 1

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

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-50ec26c596d4479b8044411e753d5487
出典データセット
uspto-grants-2013_02
特許番号
US08372842B2

反応ノート

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