Ammonium Chloride → 3-((7-Chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile

HRID 624742Notes

Reaction equation

HRID 624742 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]2[N:9]=[CH:10][CH:11]=[C:4]2[N:3]=1.[Br-].[C:13]([C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][Zn+])#[N:14].[NH4+].[Cl-]>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.CN(C=O)C>[Cl:8][C:6]1[N:5]2[N:9]=[CH:10][CH:11]=[C:4]2[N:3]=[C:2]([CH2:18][C:17]2[CH:16]=[C:15]([CH:22]=[CH:21][CH:20]=2)[C:13]#[N:14])[CH:7]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 110741545,7-Dichloropyrazolo[1,5-a]pyrimidineHCID 178509756HCID 178509756, compound

Product 1

HCID 866546533-((7-Chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrileYield 64%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To the reaction flask, 5,7-dichloropyrazolo[1,5-a]pyrimidine (452 mg, 2.4 mmol) was added along with (3-cyanobenzyl)zinc(II) bromide (6 mL, 3.75 mmol, 0.625M in DMF), Pd(PPh3)4 (110 mg, 0.1 mmol), and DMF (10 mL). The reaction was heated at 60° C. for 4 hours then cooled to room temperature. The reaction mixture was poured into saturated aqueous NH4Cl solution and ice and extracted with ethyl acetate. The combined extracts were washed with water, saturated NaCl solution, and then dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by column chromatography on silica using 35% ethyl acetate/hexanes as the eluent. The product, 3-((7-chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile, was recovered in 64% yield. LCMS (M+1=269)

Workup

  1. temperaturethen cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with water, saturated NaCl solution
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by column chromatography on silica using 35% ethyl acetate/hexanes as the eluent
  7. customThe product, 3-((7-chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile, was recovered in 64% yield

Sources & evidence

ORD record
ord-9e138917faa74b6a9fb651f55b5785bb
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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