Dimethylformamide → HCID 57978000, compound

HRID 1865825Notes

Reaction equation

HRID 1865825 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([OH:8])=[C:4]([C:9]2[CH:14]=[CH:13]C=CN=2)[C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1.C[N:23]([CH:25]=O)C.[C:27]([O-])([O-])=O.[K+].[K+].Cl[CH2:34][C:35]1[C:36]([CH3:45])=[N:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=1>CCOC(C)=O>[Cl:1][C:2]1[C:3]([C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)=[C:4]([C:9]2[CH:14]=[CH:13][N:23]=[CH:25][CH:27]=2)[C:5](=[O:8])[N:6]([CH2:34][C:35]2[C:36]([CH3:45])=[N:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=2)[N:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 598348153-(Chloromethyl)-2-methyl-6-(trifluoromethyl)pyridineHCID 178518925HCID 178518925, compound

Product 1

HCID 57978000HCID 57978000, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a round bottom flask was added 6-chloro-5-(4-chlorophenyl)-4-(pyridinyl)pyridazin-3-ol (1.1 gm, 3.47 mmol), DMF (10 ml), K2CO3 (0.958 gm, 6.94 mmol), and 3-(chloromethyl)-2-methyl-6-(trifluoromethyl)pyridine (0.798 gm, 3.817 mmol). The reaction was heated to 80° C. and stirred at that temperature for 2 hrs. The reaction was then cooled to rt and diluted with EtOAc (75 ml). The resulting mixture was poured into a separatory funnel, washed with water (4×10 ml) and with saturated aqueous NaCl (15 ml). The organic layer was then slurried with MgSO4 to remove excess water, filtered and concentrated. The crude product was purified using an automated column chromatography system (ISCO, 40 gm silica gel) eluting with a gradient of 40%-100% EtOAc/Hex to give product 6-chloro-5-(4-chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-4-(pyridin-4-yl)pyridazin-3(2H)-one as beige solid (1.35 gm, 79% yield). HPLC retention time (method A)3.140 min; LCMS (M+H)=491.1.

Workup

  1. temperatureThe reaction was then cooled to rt
  2. additionThe resulting mixture was poured into a separatory funnel
  3. washwashed with water (4×10 ml) and with saturated aqueous NaCl (15 ml)
  4. customto remove excess water
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified
  8. washeluting with a gradient of 40%-100% EtOAc/Hex

Sources & evidence

ORD record
ord-abdf1a9eed74418d8d5852b4b0af183e
Source dataset
uspto-grants-2009_12
Patent number
US07629342B2

Reaction notes

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