Potassium Phosphate, Tribasic → 6-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-amine

HRID 449647

Reaction equation

HRID 449647 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[N:15]=[N:14][C:13]([NH2:16])=[CH:12][CH:11]=1.[Cl-].[CH3:18][NH+:19]1[CH2:24][CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH2:21][CH2:20]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(O)CCC.O.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]>[CH3:18][N:19]1[CH2:20][CH:21]=[C:22]([C:10]2[N:15]=[N:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH2:23][CH2:24]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27947796-Bromopyridazin-3-amineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 667428051-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridinium chloride

Product 1

HCID 667428086-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-amineYield 82%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

In a 15 mL microwave reaction vial was added potassium phosphate tribasic (1.43 g, 6.74 mmol), 6-bromopyridazin-3-amine (335 mg, 1.93 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridinium chloride (500 mg, 1.93 mmol), X-PHOS (138 mg, 289 μmol) and bis(dibenzylideneacetone)palladium (83 mg, 144 μmol) in 7 mL n-butanol and 1.4 mL H2O. The tube was sealed under argon and heated at 115° C. in oil bath for 3 hrs then stirred at room temperature overnight. The phases were separated and the aqueous was extracted with EtOAc. (10 ml). Water (20 mL) was added to the residual aqueous phase and was extracted with DCM (3×10 mL). The extracts were combined with the EtOAc organic phase. The resultant solution was absorbed onto silica gel and purified by LC chromatography eluting with 0-10% (10% NH4OH in MeOH) in 1/1 EtOAc/hexane to afford 300 mg (82%) of the title compound.

Workup

  1. customIn a 15 mL microwave reaction
  2. customThe tube was sealed under argon
  3. customThe phases were separated
  4. extractionthe aqueous was extracted with EtOAc
  5. additionWater (20 mL) was added to the residual aqueous phase
  6. extractionwas extracted with DCM (3×10 mL)
  7. customThe resultant solution was absorbed onto silica gel
  8. custompurified by LC chromatography
  9. washeluting with 0-10% (10% NH4OH in MeOH) in 1/1 EtOAc/hexane

Sources & evidence

ORD record
ord-cafd7974e6f74ac290c8eed5ebf44287
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Linked notes

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