Hydrochloric Acid → HCID 178461577, compound

HRID 1861860Notes

Reaction equation

HRID 1861860 reaction equation
[ClH:1].[NH2:2][OH:3].C(N(CC)CC)C.Cl[C:12]1[CH:37]=[CH:36][C:15]([O:16][CH2:17][C:18]([N:20]2[CH2:25][C@@H:24]([CH3:26])[N:23]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:22][C@@H:21]2[CH3:35])=[O:19])=[C:14]([C:38]#[N:39])[CH:13]=1.Cl>CS(C)=O.O.C(OCC)(=O)C>[Cl:1][C:12]1[CH:37]=[CH:36][C:15]([O:16][CH2:17][C:18]([N:20]2[CH2:25][C@@H:24]([CH3:26])[N:23]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:22][C@@H:21]2[CH3:35])=[O:19])=[C:14]([C:38](=[NH:39])[NH:2][OH:3])[CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 69296894HCID 69296894, compound

Product 1

HCID 178461577HCID 178461577, compoundYield 12.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of hydroxylamine, hydrochloride (0.17 g, 2.5 mmol) in DMSO (3 mL) was added triethylamine (0.252 g, 2.5 mmol). The mixture was stirred at ambient temperature for 10 minutes, then filtered and washed with THF. The filtrate was concentrated in vacuo to remove the THF then treated with (trans)-1-((4-chloro-2-cyanophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine (0.200 g, 0.48 mmol). The resulting mixture was heated to 75° C. for 20 hours. At that time the mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, then brine, dried over MgSO4, filtered concentrated in vacuo to afford 0.21 9 of an oil. 0.030 g of this oil was dissolved in ethyl acetate and treated with 1 M ethereal HCl solution (excess). The resulting solid was collected by filtration and washed with ethyl acetate. Drying in vacuo afforded 0.027 g of (trans)-1-((4-chloro-2-(hydroxyamidino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine as a white solid; NMR (CDCl3) 7.6 (s, 1), 7.3 (t, 2), 7.2 (dd, 1), 7.0 (t, 2), 6.7 (br d, 1), 6.1 (br s, 2), 4.7 (m, 3), 3.7 (br d, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.7 (m, 1), 2.2 (t, 1), 1.3 (m, 3), 0.9 (m, 3) ppm.

Workup

  1. filtrationfiltered
  2. washwashed with THF
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto remove the THF
  5. temperatureThe resulting mixture was heated to 75° C. for 20 hours
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washwas washed with water
  9. dry with materialbrine, dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto afford 0.21 9 of an oil
  13. filtrationThe resulting solid was collected by filtration
  14. washwashed with ethyl acetate
  15. customDrying in vacuo

Sources & evidence

ORD record
ord-ef32c8647f6a4a0d813ec59b15a1d0cf
Source dataset
uspto-grants-2003_03
Patent number
US06534509B1

Reaction notes

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