Ammonium Chloride → HCID 68762104, compound

HRID 387606Notes

Reaction equation

HRID 387606 reaction equation
[Cl-].[CH3:2][Zn+].Br[C:5]1[C:6]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[C:7]2[CH:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[C:8]2=[N:9][CH:10]=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>[CH3:22][O:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][N:11]2[C:8]3=[N:9][CH:10]=[C:5]([CH3:2])[C:6]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:25][CH2:24]4)=[C:7]3[CH:13]=[N:12]2)=[CH:20][CH:19]=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 178477797HCID 178477797, compound

Product 1

HCID 68762104HCID 68762104, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Methylzinc (II) chloride (2M solution in THF, 1244 μL, 2.488 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 (86.25 mg, 0.07464 mmol) in THF (5 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 75° C. for 1.5 hours and allowed to cool to room temperature. The mixture was poured into a saturated aqueous NH4Cl solution (50 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40S+) eluting with 2% MeOH/CH2Cl2 to provide tert-butyl 4-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (470 mg, 0.806 mmol, 81.0% yield) as a solid. LCMS (APCI+) m/z 438.2 (M+H)+.

Workup

  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 resulting residue was purified by flash chromatography on silica gel (Biotage Flash 40S+)
  7. washeluting with 2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-5b3224feeccf4245aadb827e4a16e47f
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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