Piperazine → HCID 23655018, compound

HRID 556109Notes

Reaction equation

HRID 556109 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].O.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.CN(C=O)C>O>[CH2:1]([C:8]1[S:12][C:11]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[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 23655018HCID 23655018, compoundYield 69.5%

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, 1.77 g (20.6 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 three 3×10 ml. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a thick crude product, which was purified under a reduced pressure by silica gel column chromatography eluted with dichloromethane and methanol at a ratio 10:1-5:1 (V:V) to give a 1.05 g oily and thick product in a yield of 69.5%, 1H-NMR (CDCl3, 400 MHz) δ: 2.99 (4H, t, J=5.2 Hz, 2×CH2), 3.46 (4H, t, J=5.2 Hz, 2×CH2), 3.82 (3H, s, OCH3), 4.12 (2H, s, CH2), 6.90 (2H, d, J=8.80 Hz, ArH), 7.18˜7.35 (5H, m, ArH), 7.53 (2H, d, J=8.80 Hz, ArH); EI-MS m/e (%): 365.0 (M+, 86), 323.0 (28), 309.0 (100), 296.0 (49); HREI-MS Calcd. for C21H23N3OS: 365.1562. found: 365.1564.

Workup

  1. stirringstirred for 12 hours
  2. extractionextracted with ethyl acetate three 3×10 ml
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b21fc7df29d2434dad0e72c8b80346ef
Source dataset
uspto-grants-2011_11
Patent number
US08053581B2

Reaction notes

Loading…