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

HRID 872580Notes

Reaction equation

HRID 872580 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([NH:22][C@@H:23]([CH2:26][CH3:27])[CH2:24]O)(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:22][C@@H:23]([CH2:26][CH3:27])[CH2:24][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 11263954tert-butyl N-[(2S)-1-hydroxybutan-2-yl]carbamateHCID 178509585HCID 178509585, compound

Product 1

HCID 67170892(S)-4-(1-(2-aminobutyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrileYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Chloro-4-(1H-pyrazol-3-yl)benzonitrile (1.06 g, 4.40 mmol), N-Boc-(S)-(−)-2-amino-1-butanol (1.0 g, 5.28 mmol) and triphenylphosphine (1.73 g, 6.61 mmol) were dissolved in 15 ml of dry THF under nitrogen atmosphere. DIAD (1.73 ml; 8.81 mmol) was added slowly by syringe to cooled (0° C.) reaction mixture. After being stirred overnight at RT, the reaction mixture was evaporated to dryness. The evaporation residue was dissolved in 20 ml of 10% HCl (g)/EtOH-solution and stirred at RT overnight to induce Boc-deprotection. Solvents were evaporated and the evaporation residue was taken up in water and brine. Thus obtained solution was washed twice with DCM, made alkaline (pH˜12) by adding 2 M NaOH-solution, and extracted twice with DCM. The latter organic extracts were combined, dried over Na2SO4, filtered and evaporated to give 568 mg (47%) of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ0.87-0.94 (m, 3H), 1.10-1.45 (m, 2H), 2.97-3.05 (m. 1H), 4.01 (dd, 1H), 4.13 (dd, 1H), 4.68-4.86 (m, 1H), 6.97 (d, 1H), 7.86 (d, 1H), 7.95 (dd, 1H), 7.97 (dd, 1H), 8.10-8.12 (m, 1H). MS [M+1]: m/z [274.8+1].

Workup

  1. temperatureto cooled
  2. custom(0° C.) reaction mixture
  3. customthe reaction mixture was evaporated to dryness
  4. dissolutionThe evaporation residue was dissolved in 20 ml of 10% HCl (g)/EtOH-solution
  5. stirringstirred at RT overnight
  6. customSolvents were evaporated
  7. washThus obtained solution was washed twice with DCM
  8. additionby adding 2 M NaOH-solution
  9. extractionextracted twice with DCM
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-3cdeef4aa8a841ee940c40b38dd77128
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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