Triphenylphosphine → (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

HRID 872473Notes

Reaction equation

HRID 872473 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:14]=[CH:13][NH:12][N:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)(O[C@@H:18]([CH2:21]C(C)(C)C)[CH2:19]O)N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/[N:52]=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:52][C@@H:18]([CH3:21])[CH2:19][N:12]1[CH:13]=[CH:14][C:10]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[CH:9]=2)=[N:11]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 87120669HCID 87120669, compoundHCID 178509585HCID 178509585, compound

Product 1

HCID 67170882(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileYield 50.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Chloro-4-(1H-pyrazol-3-yl)benzonitrile (4.00 g; 19.64 mmol), (S)-tert-butyl-1-hydroxypropan-2-yl carbamate (3.79 g; 21.61 mmol) and triphenylphosphine were dissolved in dry THF under nitrogen atmosphere and stirred. Diisopropylazodicarboxylate (7.74 ml; 39.3 mmol) was added dropwise and the reaction flask was cooled by ice bath. The reaction was stirred at RT overnight (18 h) and evaporated to dryness. For Boc deprotection 200 ml of 10% HCl/EtOH solution was added to the evaporation residue, stirred for 20 h at RT and evaporated to dryness. 100 ml of water was added to the evaporation residue and washed with 3×120 ml of DCM to remove reactant residues. pH of water phase was adjusted to ˜12 by addition of 2 M NaOH, washed with 3×80 ml of DCM and organic phase dried over Na2SO4. Organic phase was filtered and evaporated to give 2.605 g of the title compound.

Workup

  1. temperaturethe reaction flask was cooled by ice bath
  2. stirringThe reaction was stirred at RT overnight (18 h)
  3. customevaporated to dryness
  4. additionFor Boc deprotection 200 ml of 10% HCl/EtOH solution was added to the evaporation residue
  5. stirringstirred for 20 h at RT
  6. customevaporated to dryness
  7. addition100 ml of water was added to the evaporation residue
  8. washwashed with 3×120 ml of DCM
  9. customto remove reactant residues
  10. additionpH of water phase was adjusted to ˜12 by addition of 2 M NaOH
  11. washwashed with 3×80 ml of DCM and organic phase
  12. dry with materialdried over Na2SO4
  13. filtrationOrganic phase was filtered
  14. customevaporated

Sources & evidence

ORD record
ord-5bc669ecc20348bbb11db2571c4c70f2
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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