Propargyl bromide → HCID 86682241, compound

HRID 1428372Notes

Reaction equation

HRID 1428372 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[C:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([CH3:21])=[N:9]2)[CH:5]=[N:6][CH:7]=1.[H-].[Na+].Br[CH2:25][C:26]#[CH:27].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[C:11]([N:13]([CH2:27][C:26]#[CH:25])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[C:10]([CH3:21])=[N:9]2)[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67499163HCID 67499163, compound

Product 1

HCID 86682241HCID 86682241, compoundYield 81.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cold solution of tert-butyl 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (1200 mg, 4.11 mmol) in dry N,N-dimethylformamide (DMF; 4 mL) under nitrogen was added 60% wt sodium hydride (197 mg, 4.93 mmol) and the mixture stirred for 10 minutes (min). 3-Bromoprop-1-yne (733 mg, 6.16 mmol) was then added and the mixture was stirred for additional 0.5 hour (h) at 0-5° C. The mixture was allowed to warm to ambient temperature and then stirred for additional 3 h. The brown reaction mixture was poured into saturated aqueous ammonium chloride (NH4Cl; 20 mL), and diluted with ethyl acetate (EtOAc; 50 mL). The organic phase was separated and the aqueous phase extracted with EtOAc (20 mL). The combined organic phase was washed with brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and concentrated in vacuo to give a brown oil. This oil was purified on silica gel eluting with mixtures of hexanes and EtOAc to give the title compound as a light yellow solid (1103 mg, 81%): mp 81-82° C.; 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H), 8.37 (d, J=2.5 Hz, 1H), 7.99 (s, 1H), 7.83 (dt, J=9.5, 2.2 Hz, 1H), 4.31 (s, 2H), 2.29 (t, J=2.4 Hz, 1H), 2.27 (s, 3H), 1.45 (s, 9H); ESIMS m/z 229.84 ([M]+).

Workup

  1. stirringthe mixture was stirred for additional 0.5 hour (h) at 0-5° C
  2. stirringstirred for additional 3 h
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with EtOAc (20 mL)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customThis oil was purified on silica gel eluting with mixtures of hexanes and EtOAc

Sources & evidence

ORD record
ord-3c936ffc3cab47bebcafe750b1fecf5f
Source dataset
uspto-grants-2015_01
Patent number
US08937083B2

Reaction notes

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