Acetonitrile → 3-(5-Cyano-6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzamide

HRID 869166Notes

Reaction equation

HRID 869166 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([CH3:12])[CH3:11])=[C:4]([C:20]#[N:21])[CH:3]=1.[NH2:22][C:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)=[O:24].C([O-])([O-])=O.[K+].[K+].CC#N>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([C:4]1[CH:3]=[C:2]([C:29]2[CH:30]=[C:25]([CH:26]=[CH:27][CH:28]=2)[C:23]([NH2:22])=[O:24])[N:7]=[N:6][C:5]=1[NH:8][CH2:9][C:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)([CH3:12])[CH3:11])#[N:21]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 2737814(3-Carbamoylphenyl)boronic acidHCID 866861346-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrile

Product 1

HCID 674530473-(5-Cyano-6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzamideYield 4.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrile (550 mg, 1.8 mmol, 1.0 equiv), 3-aminocarbonylphenylboronic acid, pinacol ester (330 mg, 2.0 mmol, 1.1 equiv) and aqueous K2CO3 (2.0 M, 5.0 mL, 5.4 mmol, 3.0 equiv) in dioxane (18 mL) was added Pd(dppf)Cl2 (150 mg, 0.18 mmol, 0.1 equiv). The mixture was stirred at 120° C. for 10 minutes in a microwave and allowed to cool to room temperature. The solvents were evaporated in vacuo, and the residue was dissolved in dichloromethane. The solution was filtered and the solvent dried over Na2SO4. Purification over silica gel using a gradient of 40-80% EtOAc/hexanes gave a yellow solid that was slurried with CH3CN to give the desired product (30 mg, 4.3%) as a yellow solid. m/z=390.2 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. customThe solvents were evaporated in vacuo
  3. dissolutionthe residue was dissolved in dichloromethane
  4. filtrationThe solution was filtered
  5. dry with materialthe solvent dried over Na2SO4
  6. customPurification over silica gel using a gradient of 40-80% EtOAc/hexanes
  7. customgave a yellow solid

Sources & evidence

ORD record
ord-e96d84480bf9419891bc92e57ba3f416
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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