Hydrazine → HCID 178509473, compound

HRID 2365754Notes

Reaction equation

HRID 2365754 reaction equation
CO[C:3](=[C:14]([C:17]#[N:18])[C:15]#[N:16])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1.[NH2:19][NH2:20]>CCO>[N+:11]([C:7]1[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=1)[CH2:4][C:3]1[C:14]([C:15]#[N:16])=[C:17]([NH2:18])[NH:20][N:19]=1)([O-:13])=[O:12]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 86659132HCID 86659132, compound

Product 1

HCID 178509473HCID 178509473, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Reagent 2-(1-methoxy-2-(3-nitrophenyl)ethylidene)malononitrile (0.97 g; 4.0 mmol) was combined with hydrazine (0.3 mL; 6.0 mmol; Sigma-Aldrich) in 10 mL EtOH for 90 minutes at room temperature. Afterwards the reaction was concentrated in vacuo, suspended in brine and extracted with chloroform (3×50 mL). The organic layer was dried over MgSO4, then filtered, and concentrated in vacuo to afford 3-(3-nitrobenzyl)-5-amino-1H-pyrazole-4-carbonitrile (ESI-MS m/z [M+H]+ found 244.5, calculated 244.1). The product was combined with formamide (1.5 mL) and heated to 160° C. overnight. H20 was added to the cooled reaction and the precipitate was filtered and dried to afford 3-(3-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 271.4, calculated 271.1). This recovered solid (50 mg, 0.19 mmol) was then added to a solution containing benzyl bromide (0.1 mL, 0.28 mmol), K2CO3 (0.125 g), DMF (1.0 mL). The reaction mixture was purged with Argon and stirred overnight at 80° C. The reaction was filtered to remove solid K2CO3, and the filtrate was combined with brine and the organic product was extracted in CH2Cl2 (3×50 mL) to afford 3-(3-nitrobenzyl)-1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 361.4, calculated 361.1). This precipitated intermediate was then mixed with excess Zinc dust, 5 mL THF, 0.4 mL HOAc for 12 hours under Argon at room temperature. Afterwards the reaction was filtered through Celite®, extracted with EtOAc and concentrated in vacuo to afford 3-(3-aminobenzyl)-1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (ESI-MS m/z [M+H]+ found 331.5, calculated 331.2). To this reduced precursor, molar equivalents of 3-(trifluoromethyl) benzoyl chloride (Sigma-Aldrich) were added drop wise in ice-cold CH2Cl2. The reaction proceeded until completion as judged by TLC, was concentrated in vacuo, resuspended in 50:50 H20-CH3CN, and purified on a C18 column in CH3CN/H20/0.1% TFA (1-100% gradient) to yield final Cmpd BB5 N-(3-((4-amino-1-benzyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)methyl)phenyl)-3-(trifluoromethyl)benzamide (ESI-MS m/z [M+H]+ found 503.4, calculated 503.2).

Workup

  1. concentrationAfterwards the reaction was concentrated in vacuo
  2. extractionextracted with chloroform (3×50 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bbb4a995d24641c28ffe787f6df72264
Source dataset
uspto-grants-2014_04
Patent number
US08697709B2

Reaction notes

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