Hydrochloric Acid → HCID 68818290, compound

HRID 734357Notes

Reaction equation

HRID 734357 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C1(C2C=C(F)[CH:24]=[CH:23][C:22]=2[C:28]([C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32][C:31]=2C2CC2)=[O:29])CC1.C(=O)([O-])[O-].[K+].[K+].[ClH:46]>CS(C)=O.CO.C(OCC)C>[ClH:46].[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:13][CH2:14][N:15]([C:33]3[CH:32]=[CH:31][C:30]([C:28]([CH:22]4[CH2:23][CH2:24]4)=[O:29])=[CH:35][CH:34]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 28282195HCID 28282195, compoundHCID 53737258Cyclopropyl-4-fluorophenyl ketone

Product 1

HCID 68818290HCID 68818290, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
140 °C

Procedure

To 1-isopropyl-4-(piperidine-4-carbonyl)-piperazine (D1)(0.25 g) and cyclopropyl-4-fluorophenyl ketone (0.3 g), dissolved in DMSO (5 ml) was added potassium carbonate (0.37 g). The reaction was heated to 140° C. for 2 h. After cooling the mixture, the inorganics were filtered off. The filtrate was diluted with MeOH (20 ml) and then poured onto a 10 g isolute SCX column which was washed with MeOH (50 ml). The product was eluted with 10% ammonia in MeOH (50 ml), and then further purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. Fractions containing the required product were evaporated to give the free base which was dissolved in MeOH (4 ml) and treated with 1N HCl in diethyl ether (2 ml) to give the title compound (E105) as a solid (51mg). 1H NMR δ [DMSO-d6]: 0.93 (4H, m) 1.27 (6H, d, J=6.4 Hz), 1.5-1.8 (2H, m), 2.77-3.14 (7H, m), 3.38-3.48 (2H, m), 3.92-4.56 (4H, m), 6.98 (2H, d, J=9.2 Hz), 7.89 (2H, d, J=9.2 Hz), 10.6 (1H, br s). MS electrospray; (+ve ion) 384 (MH+).

Workup

  1. temperatureAfter cooling the mixture
  2. filtrationthe inorganics were filtered off
  3. additionThe filtrate was diluted with MeOH (20 ml)
  4. additionpoured onto a 10 g isolute SCX column which
  5. washwas washed with MeOH (50 ml)
  6. washThe product was eluted with 10% ammonia in MeOH (50 ml)
  7. customfurther purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  8. additionFractions containing the required product
  9. customwere evaporated
  10. customto give the free base which

Sources & evidence

ORD record
ord-fc9e64f6dc854addb070e413361ddf48
Source dataset
uspto-grants-2009_09
Patent number
US07592347B2

Reaction notes

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