Potassium Phosphate, Tribasic → HCID 46191516, compound

HRID 2368168Notes

Reaction equation

HRID 2368168 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[CH:23]=2)=[CH:6][C:7]=1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1)=[O:9].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[CH3:59][N:60]1[CH:64]=[C:63](B2OC(C)(C)C(C)(C)O2)[CH:62]=[N:61]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[O:18][CH3:19])[CH2:11][NH:10][C:8]([C:7]1[CH:6]=[C:5]([C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[CH:23]=2)[N:4]=[N:3][C:2]=1[C:63]1[CH:62]=[N:61][N:60]([CH3:59])[CH:64]=1)=[O:9]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86662436HCID 86662436, compound

Product 1

HCID 46191516HCID 46191516, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
175 °C

Procedure

To a solution of 3-chloro-N-(3,4-dimethoxybenzyl)-6-(3,5-dimethylphenyl)pyridazine-4-carboxamide (1-3, 0.012 g, 0.029 mmol, 1.0 equiv) in DMF (0.20 mL) was added Pd2(dba)3 (0.0027 g, 0.003 mmol, 0.1 equiv), S-Phos (0.0024 g, 0.006 mmol, 0.2 equiv), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.036 g, 0.18 mmol, 6.0 equiv) and K3PO4 (0.025 g, 0.12 mmol, 4.0 equiv) and the reaction was heated to 175° C. for 30 minutes in the microwave. The reaction mixture was cooled and partitioned between EtOAc and water. The organic phase was washed three times with water and dried over MgSO4 and concentrated. The residue was purified by normal phase column chromatography (5 to 100% EtOAc in hexanes) and then purified by reverse phase column chromatography (5 to 85% ACN in water, 0.1% TFA buffer) to afford the product as a solid after freebasing the purified fractions. HRMS [M+H] C26H27N5O3 calc'd 458.2227. found 458.2210.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between EtOAc and water
  3. washThe organic phase was washed three times with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by normal phase column chromatography (5 to 100% EtOAc in hexanes)
  7. custompurified by reverse phase column chromatography (5 to 85% ACN in water, 0.1% TFA buffer)

Sources & evidence

ORD record
ord-70d5e44d67754c2ba7dd2e9da4bc87fb
Source dataset
uspto-grants-2014_04
Patent number
US08703770B2

Reaction notes

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