Dimethyl Sulfide → 2-{3-[4-Cyclopropylmethyl-piperazin-1-yl]-phenyl}-1-methyl-1H-benzoimidazole

HRID 2047375Notes

Reaction equation

HRID 2047375 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]4[N:22]([CH3:23])[C:21]5[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=5[N:19]=4)[CH:13]=3)[CH2:8][CH2:7]2)=O)[CH2:3][CH2:2]1.S(C)C>C1COCC1>[CH:1]1([CH2:4][N:6]2[CH2:7][CH2:8][N:9]([C:12]3[CH:13]=[C:14]([C:18]4[N:22]([CH3:23])[C:21]5[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=5[N:19]=4)[CH:15]=[CH:16][CH:17]=3)[CH2:10][CH2:11]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 68671116cyclopropyl-{4-[3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazin-1-yl}-methanone

Product 1

HCID 686701222-{3-[4-Cyclopropylmethyl-piperazin-1-yl]-phenyl}-1-methyl-1H-benzoimidazoleYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of cyclopropyl-{4-[3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazin-1-yl}-methanone (0.17 g, 0.47 mmol) in dry THF (3.50 mL) was added (CH3)2S.BH3 in THF (0.11 mL, 1.18 mmol) and the resulting suspension was heated at 65° C. overnight. The reaction solution was then cooled to room temperature, solvent was removed under reduced pressure and 1N HCl (3 mL) was added to the residue before heating at 100° C. for 6 h. The reaction was cooled to room temperature, then made basic by the dropwise addition of 15% NaOH and extracted with EtOAc (3×10 mL) The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to afford a residue that was purified by Preparative HPLC, to obtain 0.05 g (32%) of the title compound.

Workup

  1. customsolvent was removed under reduced pressure and 1N HCl (3 mL)
  2. additionwas added to the residue
  3. temperaturebefore heating at 100° C. for 6 h
  4. temperatureThe reaction was cooled to room temperature
  5. additionmade basic by the dropwise addition of 15% NaOH
  6. extractionextracted with EtOAc (3×10 mL) The combined organic layers
  7. dry with materialwere dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford a residue that
  11. customwas purified by Preparative HPLC

Sources & evidence

ORD record
ord-fa2fa52f2a02460f814678794eef5d0b
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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