(Diethylamino)sulfur trifluoride → 3'-(7-Fluoromethylimidazo[1,2-alpha]pyridin-3-yl)biphenyl-2-carbonitrile

HRID 985546Notes

Reaction equation

HRID 985546 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][N:6]2[C:9]([C:12]3[CH:13]=[C:14]([C:18]4[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:15]=[CH:16][CH:17]=3)=[CH:10][N:11]=[C:5]2[CH:4]=1.C(N(S(F)(F)[F:32])CC)C.C(=O)([O-])O.[Na+]>ClCCl>[F:32][CH2:2][C:3]1[CH:8]=[CH:7][N:6]2[C:9]([C:12]3[CH:13]=[C:14]([C:18]4[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:15]=[CH:16][CH:17]=3)=[CH:10][N:11]=[C:5]2[CH:4]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 98803563'-(7-Hydroxymethylimidazo[1,2-alpha]-pyridin3-yl)biphenyl-2-carbonitrile

Product 1

HCID 99019133'-(7-Fluoromethylimidazo[1,2-alpha]pyridin-3-yl)biphenyl-2-carbonitrileYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) suspension of 3′-(7-hydroxymethylimidazo[1,2-α]pyridin-3-yl)biphenyl-2-carbonitrile (96 mg, 0.30 mmol) in dichloromethane (20 ml) was added (diethylamino)sulfur trifluoride (50 mg, 0.31 mmol) dropwise over 5 min. The mixture was stirred at −78° C. for 20 min then allowed to warm to −40° C. for 5 min before quenching the reaction with a pre-cooled −40° C. solution of acetic acid (0.5 ml) in dichloromethane (5 ml). The mixture was warmed to ambient temperature, made basic with saturated sodium hydrogencarbonate solution (30 ml) and extracted with dichloromethane (2×75 ml). The combined organics were washed with brine (30 ml), dried over anhydrous sodium sulfate and evaporated to dryness. Purification by silica gel chromatography eluting with dichloromethane and 1% conc. ammonia on a gradient of methanol (1-2%) gave a solid which was triturated with diethyl ether to give the title compound (84 mg, 87%) as a white powder. 1H NMR (400 MHz, CDCl3) δH 5.45 (2H, d, J 47), 6.90 (1H, dd, J 7 and 2), 7.50 (1H, dt, J 8 and 1), 7.57-7.60 (2H, m), 7.61-7.72 (4H, m), 7.78-7.84 (3H, m), 8.61 (1H, dd, J 7 and 1); m/z (ES+) 328 (M++H).

Workup

  1. temperatureTo a cooled
  2. temperatureto warm to −40° C. for 5 min
  3. custombefore quenching
  4. customthe reaction with a pre-cooled −40° C. solution of acetic acid (0.5 ml) in dichloromethane (5 ml)
  5. temperatureThe mixture was warmed to ambient temperature
  6. extractionextracted with dichloromethane (2×75 ml)
  7. washThe combined organics were washed with brine (30 ml)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated to dryness
  10. customPurification by silica gel chromatography
  11. washeluting with dichloromethane and 1% conc. ammonia on a gradient of methanol (1-2%)
  12. customgave a solid which
  13. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-7a8145cc2ddf4d7ba9353ba473453bb1
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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