Dimethyl Sulfoxide → 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-imidazole

HRID 273070Notes

Reaction equation

HRID 273070 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[N:11]1([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3([C:32]4[NH:33][CH2:34][CH2:35][N:36]=4)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH2:15][CH2:14][CH2:13][CH2:12]1.C(N(CC)CC)C>ClCCl>[N:11]1([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3([C:32]4[NH:36][CH:35]=[CH:34][N:33]=4)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[CH2:12][CH2:13][CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68576326HCID 68576326, compound

Product 1

HCID 598374792-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-imidazoleYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

Dimethylsulphoxide (0.156 mL, 2.19 mmol) and dichloromethane (15 mL) were combined and cooled to −78° C. under nitrogen, oxalyl chloride (0.191 mL, 2.19 mmol) was added and the reaction mixture was stirred at −78° C. under nitrogen for 1 hour. A solution of 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}4,5-dihydro-1H-imidazole (0.314 g, 0.88 mol) in dichloromethane (15 mL) was added slowly. The reaction was stirred at −78° C. for 1 hour. Triethylamine (0.611 mL, 4.4 mmol) was then added and the reaction was stirred for a further hour. The reaction mixture allowed to warm to room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (100 mL) and washed with an aqueous ammonia solution (20 mL). The organic was dried over sodium sulphate, filtered and concentrated in vacuo to provide a yellow oil. This was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1) to provide a yellow oil, which was triturated with diethyl ether. A cream solid was filtered to provide the title compound (0.07 g, 22%). 1H NMR (400 MHz, CDCl3) δ 1.80 (m, 4H), 2.05 (m, 2H), 2.30 (m, 2H), 2.50 (m, 2H), 2.60-2.78 (m, 6H), 3.73 (m, 2H), 3.83 (m, 2H) (4.0 (t, 2H), 6.85 (d, 2H), 6.95 (s, 2H), 7.15 (d, 2H). HRMS ESI+ m/z 356.2327 [MH]+.

Workup

  1. stirringThe reaction was stirred at −78° C. for 1 hour
  2. stirringthe reaction was stirred for a further hour
  3. temperatureto warm to room temperature for 1 hour
  4. washwashed with an aqueous ammonia solution (20 mL)
  5. dry with materialThe organic was dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto provide a yellow oil
  9. customThis was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1)
  10. customto provide a yellow oil, which
  11. customwas triturated with diethyl ether
  12. filtrationA cream solid was filtered

Sources & evidence

ORD record
ord-e31fed0b642045b385623c3194e63010
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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