Ammonium Chloride → tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387524ノート

反応式

HRID 387524 の反応式
[Br-].[CH:2]1([Zn+])[CH2:4][CH2:3]1.Br[C:7]1[C:8]([N:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)=[C:9]2[CH:15]=[N:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:10]2=[N:11][CH:12]=1.[NH4+].[Cl-]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:2]1([C:7]2[C:8]([N:25]3[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH2:30]3)=[C:9]3[CH:15]=[N:14][N:13]([CH2:16][C:17]4[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=4)[C:10]3=[N:11][CH:12]=2)[CH2:4][CH2:3]1

参加物

6

反応物 3

HCID 25517Ammonium ChlorideHCID 68760849tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateHCID 178419765HCID 178419765、化合物

生成物 1

HCID 68758042tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate収率 60%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
75 °C

実験手順

Cyclopropylzinc(II) bromide (2.5 mL, 2.49 mmol) was added to a solution of tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (500 mg, 0.995 mmol) and Pd(PPh3)4 (86 mg, 0.075 mmol) in THF (5 mL) under N2. The reaction mixture was heated at 75° C. (oil bath) under N2 atmosphere for 18 hours. The reaction mixture was then allowed to cool to room temperature and poured into saturated aqueous NH4Cl (50 mL) solution and extracted with EtOAc (3×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by C-18 reverse phase chromatography (Biotage 25M+) on Biotage SP4 unit using a 15-90% CH3CN/water gradient (14 CV). The fractions containing the product were pooled, and the solvents were removed. The residue was evaporated from CH3CN (3×20 mL) and dried to provide tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (275 mg, 60% yield) as a solid. LCMS (APCI+) m/z 464.2 (M+H)+, Rt=4.32 minutes.

後処理

  1. temperatureto cool to room temperature
  2. extractionextracted with EtOAc (3×50 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by C-18 reverse phase chromatography (Biotage 25M+) on Biotage SP4 unit
  8. additionThe fractions containing the product
  9. customthe solvents were removed
  10. customThe residue was evaporated from CH3CN (3×20 mL)
  11. customdried

出典と根拠

ORDレコード
ord-0a4a03a50b1744dab32ef1c8f5ebec73
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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