Piperazine → 2-(4-Isopropylpiperazin-1-yl)benzothiazole-6-carbonitrile

HRID 1944656Notes

Reaction equation

HRID 1944656 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.[I-].[Na+].C(N(CC)CC)C.Br[CH:29]([CH3:31])[CH3:30]>CN(C=O)C.O>[CH:29]([N:13]1[CH2:18][CH2:17][N:16]([C:2]2[S:3][C:4]3[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:15][CH2:14]1)([CH3:31])[CH3:30]

Participants

8

Reactant 5

HCID 4837Piperazine2×HCID 5238Sodium IodideHCID 63582-BromopropaneHCID 8471TriethylamineHCID 219858592-Chloro-1,3-benzothiazole-6-carbonitrile

Product 1

HCID 237287892-(4-Isopropylpiperazin-1-yl)benzothiazole-6-carbonitrileYield 42.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent4×

Procedure

A solution of 2-chlorobenzothiazole-6-carbonitrile (14.9 g, 0.077 mol) in DMF (250 mL) was added drop-wise at 10° C. to a mixture of anhydrous piperazine (60 g, 0.698 mol) and DMF (300 mL). Then the mixture was stirred for 2 h. Water (1,550 mL) was added and the mixture was extracted with dichloromethane (5×500 mL). The combined organic extracts was washed with water (6×500 mL), dried (Na2SO4), filtered and evaporated to give a residue which was re-crystallised from ethyl acetate. This afforded 10.5 g (56%) of 2-(piperazin-1-yl)benzothiazole-6-carbonitrile. A mixture of this piperazine derivative (19.4 g, 0.08 mol), sodium iodide (1.94 g), triethylamine (9.6 g, 0.095 mol) and DMF (80 mL) was heated with stirring to give a red liquid. A solution of 2-bromopropane (14.7 g, 0.12 mol) in DMF (80 mL) was added drop-wise at 117° C. within in 1 h. The reaction mixture was stirred at 110-117° C. for another 3 h and then allowed to cool to room temperature. Water (110 mL) was added and the mixture was filtered. The filter cake was washed until the filtrate was colourless and then dried. The solid was dissolved in DMF (250 mL) and filtered to remove a solid residue. Water (1000 mL) was added to the filtrate with stirring to give a precipitate. The solid was isolated, washed with water and dried to give 9.4 g (41%) of 2-(4-Isopropylpiperazin-1-yl)benzothiazole-6-carbonitrile.

Workup

  1. extractionthe mixture was extracted with dichloromethane (5×500 mL)
  2. washThe combined organic extracts was washed with water (6×500 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give a residue which
  7. customwas re-crystallised from ethyl acetate
  8. temperaturewas heated
  9. stirringwith stirring
  10. customto give a red liquid
  11. stirringThe reaction mixture was stirred at 110-117° C. for another 3 h
  12. filtrationthe mixture was filtered
  13. washThe filter cake was washed until the filtrate
  14. customdried
  15. dissolutionThe solid was dissolved in DMF (250 mL)
  16. filtrationfiltered
  17. customto remove a solid residue
  18. additionWater (1000 mL) was added to the filtrate
  19. stirringwith stirring
  20. customto give a precipitate
  21. customThe solid was isolated
  22. washwashed with water
  23. customdried

Sources & evidence

ORD record
ord-f7f954a39c784af2b2f1f32c24927dfd
Source dataset
uspto-grants-2013_03
Patent number
US08394842B2

Reaction notes

Loading…