Piperazine → HCID 10133817, compound

HRID 1966044Notes

Reaction equation

HRID 1966044 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:7]([C:9]1[CH:10]=[CH:11][C:12]([O:19][C:20]2[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[CH:21]=2)=[C:13]([S:15](Cl)(=[O:17])=[O:16])[CH:14]=1)#[N:8]>C(Cl)Cl>[CH3:26][C:24]1[CH:25]=[C:20]([CH:21]=[C:22]([CH3:27])[CH:23]=1)[O:19][C:12]1[CH:11]=[CH:10][C:9]([C:7]#[N:8])=[CH:14][C:13]=1[S:15]([N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)(=[O:17])=[O:16]

Participants

4

Reactant 2

HCID 4837PiperazineHCID 59549116HCID 59549116, compound

Product 1

HCID 10133817HCID 10133817, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of piperazine (16.144 g, 186.4 mmol) in CH2Cl2 (80 mL) stirred in an ice-brine bath was added dropwise of a solution of compound 23 (3.009 g, 9.35 mmol) in CH2Cl2 (270 mL) over the course of two days. The reaction was then stirred for 74 hrs, whereupon the starting material was consumed (TLC, 5% MeOH in CH2Cl2). The reaction mixture was partitioned between CH2Cl2 and water. The organic layer was then washed with saturated sodium chloride solution and dried over anhydrous MgSO4. The organic layer was then concentrated in vacuo, redissolved in a minimal amount of CH2Cl2, and chromatographed over normal phase silica (MeOH/CH2Cl2). The fractions containing the desired product were combined and concentrated in vacuo to yield an light yellow oil. The oil was then triturated with CH2Cl2/diisopropyl ether and vacuum filtered to afford compound 24 as a white powder (2.032 g, 58.5% yield, 95.5% HPLC purity). 1H NMR (500 MHz, DMSO-d6): δ 8.21 (d, J=2 Hz, 1H), 8.03 (dd, J1=9 Hz, J2=2 Hz, 1H), 7.01 (m, 1H), 6.96 (d, J=11 Hz, 1H), 6.80 (d, J=9 Hz, 2H), 3.19 (m, 2H), 3.11 (m, 2H), 2.70 (m, 2H), 2.46 (m, 2H), 2.30 (s, 1H), 2.27 (s, 6H).

Workup

  1. customwas consumed (TLC, 5% MeOH in CH2Cl2)
  2. customThe reaction mixture was partitioned between CH2Cl2 and water
  3. washThe organic layer was then washed with saturated sodium chloride solution
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationThe organic layer was then concentrated in vacuo
  6. dissolutionredissolved in a minimal amount of CH2Cl2
  7. customchromatographed over normal phase silica (MeOH/CH2Cl2)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated in vacuo
  10. customto yield an light yellow oil
  11. customThe oil was then triturated with CH2Cl2/diisopropyl ether and vacuum
  12. filtrationfiltered

Sources & evidence

ORD record
ord-f6de8ee5bc9e454ab796e89e365fe380
Source dataset
uspto-grants-2013_04
Patent number
US08420639B2

Reaction notes

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