Water → 1-{3-[6-Chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-yl]-1-oxopropyl}-4-(phenylmethyl)-4-piperidinol

HRID 1016655Notes

Reaction equation

HRID 1016655 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10](/[CH:20]=[CH:21]/[C:22]([N:24]3[CH2:29][CH2:28][C:27]([CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)([OH:30])[CH2:26][CH2:25]3)=[O:23])=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[N:12]=2)[CH:9]=1.O>N1C=CC=CC=1.CO>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([CH2:20][CH2:21][C:22]([N:24]3[CH2:25][CH2:26][C:27]([CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)([OH:30])[CH2:28][CH2:29]3)=[O:23])=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[N:12]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydride2×HCID 18407035(E)-1-{3-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-yl]-1-oxo-2-propenyl}-4-(phenylmethyl)-4-piperidinol

Product 1

HCID 101421591-{3-[6-Chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-yl]-1-oxopropyl}-4-(phenylmethyl)-4-piperidinol

Reagents, catalysts & solvents 1

HCID 22021344Pyridine methanolSolvent

Procedure

Sodium borohydride (30 mg, 0.8 mmol) was added to a solution of (E)-1-{3-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-yl]-1-oxo-2-propenyl}-4-(phenylmethyl)-4-piperidinol (Description 20, 40 mg, 0.08 mmol) in pyridine/methanol (3:1, 4 mL) and the mixture was stirred under reflux for 2 h. Further portions of sodium borohydride (30 mg, 0.8 mmol) were added and the reaction was monitored by mass spectrometry until no starting material remained. The mixture was cooled, poured into water (75 mL) and extracted with ethyl acetate (3×25 mL). The combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (35:65). The residue was recrystallised from ethanol/water and the solid was collected and dried in vacuo to give the title compound as a colorless solid. 1H NMR (360 MHz, CDCl3) δ 8.18 (1H, d, J 1.5 Hz), 7.74 (2H, d, J 8.5 Hz), 7.56 (1H, d, J 9.6 Hz), 7.44 (2H, d, J 8.5 Hz), 7.30 (3H, m), 7.15 (3H, m), 4.40 (1H, m), 3.47 (2H, m), 3.43 (1H, m), 3.24 (1H, m), 2.92 (1H, m), 2.68 (2H, s), 2.64 (2H, t, J 7.5 Hz), 1.46 (2H, m), and 1.24 (2H, m). m/z (ES+) 508, 510 (M+1).

Workup

  1. temperatureunder reflux for 2 h
  2. temperatureThe mixture was cooled
  3. extractionextracted with ethyl acetate (3×25 mL)
  4. washThe combined organic fractions were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with isohexane/EtOAc (35:65)
  9. customThe residue was recrystallised from ethanol/water
  10. customthe solid was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-3cf3d135450e43a6b10476975c8c9054
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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