HCID 59837433, compound → HCID 59837415, compound

HRID 273032Notes

Reaction equation

HRID 273032 reaction equation
CS[C:3]1[N:4]([CH2:8][C:9]2([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:17][CH:16]=3)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][N:7]=1>CCO.O.[Ni]>[N:25]1([CH2:24][CH2:23][CH2:22][O:21][C:18]2[CH:19]=[CH:20][C:15]([C:9]3([CH2:8][N:4]4[CH:5]=[CH:6][N:7]=[CH:3]4)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)=[CH:16][CH:17]=2)[CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

5

Reactant 1

HCID 59837433HCID 59837433, compound

Product 1

HCID 59837415HCID 59837415, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 2-(methylthio)-1-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methyl)-1H-imidazole (90 mg, 0.22 mmol) in EtOH (4 ml) and water (1 ml) was added Raney Nickel (50% slurry in water) in 200 mg aliquots every 30 min. After 3 h all starting material had been consumed. The mixture was filtered through Arbocel® with EtOH (200 ml) and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (90:10:1) to provide the title compound as a yellow oil (29 mg, 0.078 mmol, 36%). 1H NMR (400 MHz, CDCl3) δ 1.80-2.00 (m, 6H), 2.10 (m, 4H), 2.70-2.90 (m, 6H), 3.50 (t, 2H), 3.81 (m, 2H), 3.97 (s, 2H), 4.04 (t, 2H), 6.32 (s, 1H), 6.80-6.90 (m, 4H), 6.98 (d, 2H). HRMS ESI+ m/z 370.2485 [MH]+.

Workup

  1. customAfter 3 h all starting material had been consumed
  2. filtrationThe mixture was filtered through Arbocel® with EtOH (200 ml)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (90:10:1)

Sources & evidence

ORD record
ord-255b7bab361442b3b687cd6eca1c832e
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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