3-Chloro-6-methylpyridazine → tert-butyl 2-(6-methylpyridazin-3-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

HRID 1713162Notes

Reaction equation

HRID 1713162 reaction equation
[NH:1]1[C:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5][C:4]=2[CH:3]=[N:2]1.Cl[C:18]1[N:19]=[N:20][C:21]([CH3:24])=[CH:22][CH:23]=1.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=CC=CC=2)=C(C(C)C)C=1)C.CC([O-])(C)C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:24][C:21]1[N:20]=[N:19][C:18]([N:2]2[CH:3]=[C:4]3[CH2:5][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH2:8][C:9]3=[N:1]2)=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 2272543-Chloro-6-methylpyridazineHCID 103986805-Boc-1,4,6,7-tetrahydropyrazolo[4,3-C]pyridineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxide

Product 1

HCID 57356885tert-butyl 2-(6-methylpyridazin-3-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate (3.72 g, 16.67 mmol), 3-chloro-6-methylpyridazine (3.2 g, 24.92 mmol), Pd2(dba)3 (760 mg, 0.83 mmol), tBuXPhos (705 mg, 1.66 mmol) and tBuONa (1.99 g, 20.77 mmol) in toluene (90 mL) is degassed by argon and heated at 120° C. in a sealed tube overnight. EtOAc (200 mL) and water (250 mL) are added and the layers are separated. The organic layer is washed with water (200 mL) and then brine (200 mL), dried and evaporated. Purification of the residue by flash column with hexane/EtOAc (2:1) gives a white solid that is a mixture of two regioisomers. Recrystallization of the solid from hexane/EtOAc (1:1) gives the title compound as white needles. MS (M+1): 316.2.

Workup

  1. customis degassed by argon
  2. additionEtOAc (200 mL) and water (250 mL) are added
  3. customthe layers are separated
  4. washThe organic layer is washed with water (200 mL)
  5. dry with materialbrine (200 mL), dried
  6. customevaporated
  7. customPurification of the residue by flash column with hexane/EtOAc (2:1)
  8. customgives a white solid
  9. additiona mixture of two regioisomers
  10. customRecrystallization of the solid from hexane/EtOAc (1:1)

Sources & evidence

ORD record
ord-fa56d7a485d34fa0aadcd433f786903d
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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