Trifluoroacetic acid → HCID 86597225, compound

HRID 2056542Notes

Reaction equation

HRID 2056542 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][CH:9]([CH3:27])[CH2:10][CH2:11][NH:12][C:13]([C:15]1[N:16]=[N:17][C:18]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:19][CH:20]=1)=[O:14].[F:28][C:29]([F:37])([F:36])[CH2:30][CH:31]([CH3:35])[C:32](O)=[O:33].N12CCCN=C1CCCCC2.CN(C)CCCN=C=NCC>CN(C=O)C.C(OCC)(=O)C>[CH3:8][CH:9]([CH3:27])[CH2:10][CH2:11][NH:12][C:13]([C:15]1[N:16]=[N:17][C:18]([N:21]2[CH2:26][CH2:25][N:24]([C:32](=[O:33])[CH:31]([CH3:35])[CH2:30][C:29]([F:37])([F:36])[F:28])[CH2:23][CH2:22]2)=[CH:19][CH:20]=1)=[O:14]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27755364,4,4-Trifluoro-2-methylbutanoic acidHCID 668493226-Piperazin-1-yl-pyridazin-3-carboxylic acid (3-methylbutyl)amide

Product 1

HCID 86597225HCID 86597225, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of TFA salt of 6-piperazin-1-yl-pyridazine-3-carboxylic acid (3-methylbutyl)amide (100 mg, 0.25 mmol), 4,4,4-trifluoro-2-methylbutyric acid (47.8 mg, 0.31 mmol), 1,8-diazabicylco[5.4.0]undec-7-ene (77.8 mg, 0.51 mmol) and 1-hydroxybenozotriazole hydrate (41.4 mg, 0.31 mmol) in DMF (2 mL) was stirred at ambient temperature for 15 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (47.6 mg, 0.31 mmol) was added to this solution. The reaction mixture was stirred at ambient temperature overnight and then diluted with ethyl acetate (50 mL) and washed with aqueous saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL). The organic extract was dried over anhydrous Na2SO4, concentrated, and then purified by column chromatography eluted with hexanes:ethyl acetate (1:2). The product was obtained as a white flaky solid (80 mg, 75% yield). 1H NMR (300 MHz, CDCl3) δ8.07, 7.85, 7.01, 3.60-4.00, 3.50, 3.15, 2.80, 2.21, 1.70, 1.50, 1.25, 0.95. MS (ES+) m/z 416 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature overnight
  2. washwashed with aqueous saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. custompurified by column chromatography
  7. washeluted with hexanes:ethyl acetate (1:2)

Sources & evidence

ORD record
ord-65d218b9132340e5be0bbbf6caffa5b3
Source dataset
uspto-grants-2008_02
Patent number
US07335658B2

Reaction notes

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