Hydrochloric Acid → 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine

HRID 512716Notes

Reaction equation

HRID 512716 reaction equation
[Cl:1][C:2]1[C:6]([NH:7][C:8](=O)[CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.B(F)(F)F.CCOCC.[BH4-].[Na+].Cl.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.O1CCCC1>[Cl:1][C:2]1[C:6]([NH:7][CH2:8][CH3:9])=[CH:5][N:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 118023019N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide

Product 1

HCID 674989573-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amineYield 79%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A 100 mL 3-neck round bottom flask was charged with N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (475 mg, 2.01 mmol) and tetrahydrofuran (10 mL). borontrifluoride etherate (0.63 mL, 5.02 mmol) was added and the mixture was stirred for 15 minutes to give a suspension. Sodium borohydride (228 mg, 6.02 mmol) was added and the reaction was heated at 60° C. for 4 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate, sample was prepared by treatment of reaction mixture with hydrochloric acid, followed by sodium bicarbonate basification and ethyl acetate extraction] indicated that the reaction was complete. Water (10 mL) and concentrated hydrochloric acid (1 mL) were added and the reaction was heated at 60° C. for 1 hour. The reaction mixture was cooled to room temperature and distilled to remove tetrahydrofuran. The mixture was neutralized with saturated aqueous sodium bicarbonate to pH˜8 to afford a suspension, which was stirred for 1 hour and filtered. The filter cake was rinsed with water (10 mL) and dried under vacuum to afford a white solid (352 mg, 79%): mp 93-96° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (d, J=2.7 Hz, 1H), 8.44 (dd, J=4.6, 1.4 Hz, 1H), 8.10 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 8.06 (s, 1H), 7.50 (dd, J=8.4, 4.7 Hz, 1H), 4.63 (t, J=6.0 Hz, 1H), 3.06-2.92 (m, 2H), 1.18 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ 146.17, 138.31, 135.81, 132.82, 130.84, 124.10, 123.96, 112.23, 40.51, 14.28; EIMS m/z 222 ([M]+).

Workup

  1. customto give a suspension
  2. temperatureThe reaction mixture was cooled to room temperature
  3. distillationdistilled
  4. customto remove tetrahydrofuran
  5. customto afford a suspension, which
  6. stirringwas stirred for 1 hour
  7. filtrationfiltered
  8. washThe filter cake was rinsed with water (10 mL)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-d49b8752ab804ce886aef94fbdc1dad8
Source dataset
uspto-grants-2015_08
Patent number
US09102654B2

Reaction notes

Loading…