Diisopropylethylamine → HCID 59559650, compound

HRID 1178111Notes

Reaction equation

HRID 1178111 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:10]=[N:11][NH:12][CH:13]=1.CCN(C(C)C)C(C)C.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.[NH2:36][CH2:37][C:38]([N:40]1[CH2:45][CH2:44][N:43]([C:46](=[O:58])[C:47]2[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:48]=2[C:54]([F:57])([F:56])[F:55])[CH2:42][CH2:41]1)=[O:39]>C(Cl)Cl.O>[F:53][C:51]1[CH:50]=[CH:49][C:48]([C:54]([F:55])([F:57])[F:56])=[C:47]([CH:52]=1)[C:46]([N:43]1[CH2:42][CH2:41][N:40]([C:38](=[O:39])[CH2:37][NH:36][C:24]([N:12]2[CH:13]=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[F:2])[CH:10]=[N:11]2)=[O:26])[CH2:45][CH2:44]1)=[O:58]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 669531292-Amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]ethanone hydrochlorideHCID 66953451HCID 66953451, compound

Product 1

HCID 59559650HCID 59559650, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 4-(2-fluoro-phenyl)-1H-pyrazolehydrochloride salt (prepared by the method described above) (50 mg, 0.25 mmol), DIPEA (85 mg, 0.115 ml, 0.66 mmol) and DCM (1.5 ml) was added to a stirred solution of triphosgene (30 mg, 0.1 mmol) in DCM (2.5 mL) at room temperature. After 30 minutes, to the above solution, a mixture of 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (prepared by the method described above) (102 mg, 0.27 mmol), DIPEA (85 mg, 0.115 ml, 0.66 mmol) and DCM (1.5 ml) was added and the resulting mixture was stirred at room temperature for 1 hr. Cold water was then added and the product was extracted with DCM and the organic layer was washed with 10% HCl solution, saturated sodium bicarbonate solution and brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 50% EtOAc in Hexane as eluent) to afford 59 mg (45% yield) 4-(2-fluoro-phenyl)-pyrazole-1-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 95.23%. 1H NMR (CDCl3): δ 8.6 (t, 1H), 8.0 (m, 2H), 7.8 (m, 1H), 7.6 (t, 1H), 7.3 (m, 1H), 7.2-7.0 (m, 3H), 4.36-4.2 (m, 2H), 4.1-3.8 (m, 1H), 3.8-3.46 (m, 4H), 3.6 (t, 1H), 3.3-3.2 (m, 2H).

Workup

  1. customprepared by the method
  2. customprepared by the method
  3. additionwas added
  4. extractionthe product was extracted with DCM
  5. washthe organic layer was washed with 10% HCl solution, saturated sodium bicarbonate solution and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto get the residue
  9. customThe obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 50% EtOAc in Hexane as eluent)

Sources & evidence

ORD record
ord-3405976be71749a5aed17f1dee84748a
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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