Piperazine → HCID 57991586, compound

HRID 556111Notes

Reaction equation

HRID 556111 reaction equation
[CH2:1]([C:8]1[S:12][C:11](Cl)=[N:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[Li].[OH2:24].[NH:25]1[CH2:30][CH2:29]N[CH2:27][CH2:26]1.CN(C=[O:35])C>O>[CH2:1]([C:8]1[S:12][C:11]([N:25]([CH2:30][CH2:29][OH:35])[CH2:26][CH2:27][OH:24])=[N:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 4837PiperazineHCID 6228DimethylformamideHCID 168937Lithium hydroxide, monohydrateHCID 66986106HCID 66986106, compound

Product 1

HCID 57991586HCID 57991586, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To 25 ml eggplant-shaped bottle were added 1.30 g (4.12 mmol) 5-benzyl-2-chloro-4-(4-methoxy-phenyl)-thiazole prepared in the step 1 of Example 70, 0.35 g (8.24 mmol) LiOH.H2O, 20 mg KI, 0.87 g (8.24 mmol) piperazine, 5 ml DMF and 0.5 ml water. The mixture was stirred until homogeneous, heated to 100° C., stirred for 12 hours, added 20 ml water, and extracted with ethyl acetate 3×10 ml. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product as a off-white solid, which was purified under a reduced pressure by silica gel column chromatography eluted with dichloromethane and methanol at a ratio 10:1 (V:V) to give an oily and thick product, which was recrystallized with petroleum ether and ethyl acetate to obtain a 0.98 g white solid in a yield of 62.0%, mp: 119-120 └. 1H-NMR (CDCl3, 400 MHz) δ: 3.62 (4H, t, J=5.2 Hz, 2×CH2), 3.81 (3H, s, OCH3), 3.88 (4H, t, J=5.2 Hz, 2×CH2), 4.09 (2H, s, CH2), 6.90 (2H, d, J=8.80 Hz, ArH), 7.18˜7.35 (5H, m, ArH), 7.48 (2H, d, J=8.80 Hz, ArH); EI-MS m/e (%): 384.1 (M+, 80), 353.1 (64), 309.0 (100), 295.1 (15); HREI-MS Calcd. for C21H24N2O3S: 384.1508. found: 384.1504. Anal. Calcd. for C21H24N2O3S: C, 65.60; H, 6.29; N, 7.29. found: C, 65.42; H, 6.56; N, 7.34.

Workup

  1. stirringstirred for 12 hours
  2. extractionextracted with ethyl acetate 3×10 ml
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto obtain a crude product as a off-white solid, which
  8. customwas purified under a reduced pressure by silica gel column chromatography
  9. washeluted with dichloromethane and methanol at a ratio 10:1 (V:V)
  10. customto give an oily and thick product, which
  11. customwas recrystallized with petroleum ether and ethyl acetate

Sources & evidence

ORD record
ord-964c17d985604b9d8ce44b2046d707e6
Source dataset
uspto-grants-2011_11
Patent number
US08053581B2

Reaction notes

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