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

HRID 387610Notes

Reaction equation

HRID 387610 reaction equation
[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

Participants

6

Reactant 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, compound

Product 1

HCID 68758042tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 59.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

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, see Example 1) and Pd(PPh3)4 (86 mg, 0.075 mmol) in THF (5 mL) under nitrogen, and the reaction mixture was heated to 75° C. (oil bath) for 18 hours under a nitrogen atmosphere. Then the reaction mixture was allowed to cool to room temperature and poured into a saturated aqueous NH4Cl (50 mL) solution and extracted with EtOAc (3×50 mL). The crude product was purified by C-18 reverse phase flash chromatography (Biotage 25M+) using a gradient of 15-90% CH3CN/water on Biotage SP4 unit to provide tert-butyl 4-(5-cyclopropyl-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (275 mg, 0.59 mmol, 59.6% yield) as a solid. LCMS (APCI+) m/z 464.2 (M+H).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with EtOAc (3×50 mL)
  3. customThe crude product was purified by C-18 reverse phase flash chromatography (Biotage 25M+)

Sources & evidence

ORD record
ord-440b2b4d4b5c49ffb92491fa4f532389
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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