4-Chloroaniline → 6-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (4-CHLOROPHENYL)AMIDE

HRID 2056608Notes

Reaction equation

HRID 2056608 reaction equation
ClC1N=C(OC)N=C(OC)N=1.[F:12][C:13]([F:38])([F:37])[C:14]1[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=1[C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[N:28][C:27]([C:30]([OH:32])=O)=[CH:26][CH:25]=2)[CH2:20][CH2:19]1)=[O:17].CN1CCOCC1.[Cl:46][C:47]1[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][CH:48]=1>C1COCC1.C(OCC)(=O)C>[Cl:46][C:47]1[CH:53]=[CH:52][C:50]([NH:51][C:30]([C:27]2[N:28]=[N:29][C:24]([N:21]3[CH2:20][CH2:19][N:18]([C:16](=[O:17])[C:15]4[CH:33]=[CH:34][CH:35]=[CH:36][C:14]=4[C:13]([F:37])([F:12])[F:38])[CH2:23][CH2:22]3)=[CH:25][CH:26]=2)=[O:32])=[CH:49][CH:48]=1

Participants

7

Reactant 4

HCID 78124-ChloroanilineHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 454873706-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid

Product 1

HCID 160350036-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (4-CHLOROPHENYL)AMIDEYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-Chloro-4,6-dimethoxy-1,3,5-triazine (0.105 g, 0.60 mmol) was added to a cooled (0° C.) solution of 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (0.190 g, 0.50 mmol) and methylmorpholine (0.07 mL, 0.63 mmol) in THF (10 mL). The reaction mixture was stirred at 0° C. for 15 min, and then at ambient temperature for 1 h. 4-Chloroaniline (0.0765 g, 0.60 mmol) was then added. After stirring at ambient temperature for 20 h, the reaction mixture was diluted with ethyl acetate (100 mL), washed with water, brine, dried over anhydrous Na2SO4 and concentrated. Purification by flash chromatography and recrystallization from ethyl acetate/hexanes afforded the title compound in 67% yield (0.164 g). 1H NMR (300 MHz, CDCl3) δ 9.79, 8.08, 7.82-7.55, 7.36-7.28, 7.02, 4.10-4.00, 3.93-3.68, 3.35. 13C NMR (75 MHz, CDCl3) δ 167.6, 160.7, 160.0, 144.8, 136.2, 134.2, 132.4, 129.5, 129.2, 129.1, 127.2, 126.9, 126.8, 126.7, 125.4, 121.8, 120.7, 112.6, 46.3, 44.5, 44.3, 41.2. MS (ES+) m/z 490.1 (M+1).

Workup

  1. waitat ambient temperature for 1 h
  2. stirringAfter stirring at ambient temperature for 20 h
  3. washwashed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customPurification
  7. customby flash chromatography and recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-a573a3a22c884822a173ec16fb361253
Source dataset
uspto-grants-2008_02
Patent number
US07335658B2

Reaction notes

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