Dimethyl Sulfoxide → HCID 53325403, compound

HRID 2425518Notes

Reaction equation

HRID 2425518 reaction equation
[CH3:1][S:2]([CH3:4])=[O:3].CN(P(N(C)C)(N(C)C)=O)C.[Li]CCCC.Br[CH2:22][C:23]1[C:24]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[N:25][C:26]2[C:31]([C:32]=1[C:33]([NH:35][C@H:36]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:37][CH3:38])=[O:34])=[CH:30][CH:29]=[CH:28][CH:27]=2>C1COCC1>[CH3:1][S:2]([CH2:4][CH2:22][C:23]1[C:24]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[N:25][C:26]2[C:31]([C:32]=1[C:33]([NH:35][C@H:36]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH2:37][CH3:38])=[O:34])=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:3]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 12679HexamethylphosphoramideHCID 16064396HCID 16064396, compoundHCID 178418339Butyllithium

Product 1

HCID 53325403HCID 53325403, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of DMSO (0.075 mL, 1.05 mmol) and HMPA (0.38 mL, 2.2 mmol) in anhydrous THF (3 mL) was prepared under N2 and cooled to −78° C. To this was added a solution of n-BuLi (0.71 mL, 1.6 M in hexanes, 1.13 mmol), the reaction allowed to stir for 10 min., then 3-(bromomethyl)-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide (8) (200 mg, 0.44 mmol) was added as a solution in anhydrous THF (1 mL). The reaction was allowed to stir 10 min., additional anhydrous THF (1 mL) added, and reaction allowed stirring another 10 min. The cooling bath was then removed, saturated aqueous NH4CI (1 mL), H2O (1 mL), and Et2O (1 mL) added, the layers shaken together, and then separated. The organics were then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc/CH2Cl2) to give the desired product (170 mg, 85% yield) as a solid. 1H NMR (300 MHz, CDCl3, 52° C.) δ 8.10 (d, J=8.0 Hz, 1H), 7.86-7.61 (m, 2H), 7.55-7.25 (m, 12H), 5.29-5.16 (m, 1H), 3.44-3.07 (m, 2H), 2.73-2.37 (m, 2H), 2.27-2.15 (m, 3H), 2.15-1.86 (m, 2H), 1.02 (t, J=7.4 Hz, 3H); LCMS: m/z 457 (MH+). HRMS m/z 457.1927, calcd. 457.1950.

Workup

  1. stirringto stir 10 min.
  2. customreaction
  3. stirringallowed stirring another 10 min
  4. customThe cooling bath was then removed
  5. additionsaturated aqueous NH4CI (1 mL), H2O (1 mL), and Et2O (1 mL) added
  6. stirringthe layers shaken together
  7. customseparated
  8. dry with materialThe organics were then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography (EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-99a970235e6f4b8594e3a5b859ad7c39
Source dataset
uspto-grants-2011_06
Patent number
US07964733B2

Reaction notes

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