Hydrochloric Acid → (S)-4-(1-(1-aminopropan-2-yl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

HRID 872729Notes

Reaction equation

HRID 872729 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]=[C:6]([F:15])[C:3]=1[C:4]#[N:5].[C:16]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:21]=CC=C[CH:17]=1.CC(OC(/[N:41]=N/C(OC(C)C)=O)=O)C.Cl>C(OCC)(=O)C.C(Cl)Cl.O>[NH2:41][CH2:17][C@@H:16]([N:12]1[CH:13]=[CH:14][C:10]([C:8]2[CH:7]=[C:6]([F:15])[C:3]([C:4]#[N:5])=[C:2]([Cl:1])[CH:9]=2)=[N:11]1)[CH3:21]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 178510273HCID 178510273, compound

Product 1

HCID 67171415(S)-4-(1-(1-aminopropan-2-yl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrileYield 31.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-chloro-6-fluoro-4-(1H-pyrazol-3-yl)benzonitrile (5.0 g, 22.56 mmol), N-t-BOC-(R)-1-amino-2-propanol (7.91 g, 45.1 mmol) and triphenylphosphine (11.84 g, 45.1 mmol) were dissolved in dry ethyl acetate under nitrogen atmosphere and stirred. DIAD (9.12 g, 45.1 mmol) was added dropwise and the reaction flask was cooled by ice bath. The reaction was stirred at RT overnight. Water and concentrated HCl (18.53 ml, 226 mmol) were added to the reaction mixture and the reaction was stirred at RT overnight. Water and DCM were added to the reaction mixture, stirred and water phase was separated. Organic phase was extracted twice with water and water phases were combined. The combined water phase was washed twice with DCM and pH of water was adjusted to ˜12 by addition of NaOH. Water phase was extracted twice with DCM and combined DCM phase was washed twice with water. Organic phase was evaporated to dryness and the product was purified by Flash-chromatography. Yield 31.8%. 1H-NMR (400 MHz; DMSO): δ 1.42 (d, 3H), 2.80-3.00 (m, 2H), 4.27-4.38 (m, 1H), 7.03 (d, 1H), 7.84-7.95 (m, 2H), 8.00 (m, 1H).

Workup

  1. temperaturethe reaction flask was cooled by ice bath
  2. stirringThe reaction was stirred at RT overnight
  3. stirringthe reaction was stirred at RT overnight
  4. stirringstirred
  5. customwater phase was separated
  6. extractionOrganic phase was extracted twice with water and water phases
  7. washThe combined water phase was washed twice with DCM and pH of water
  8. additionwas adjusted to ˜12 by addition of NaOH
  9. extractionWater phase was extracted twice with DCM and combined DCM phase
  10. washwas washed twice with water
  11. customOrganic phase was evaporated to dryness
  12. customthe product was purified by Flash-chromatography

Sources & evidence

ORD record
ord-180d5e4ad5eb42119807ccc003cc9425
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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