3,6-Dichloropyridazine → Methyl(3S,4R)-4-(2,4-difluorophenyl)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylate

HRID 884031Notes

Reaction equation

HRID 884031 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][NH:12][CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15].CCN(C(C)C)C(C)C.[Cl:27][C:28]1[N:29]=[N:30][C:31](Cl)=[CH:32][CH:33]=1>O1CCOCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][N:12]([C:31]2[N:30]=[N:29][C:28]([Cl:27])=[CH:33][CH:32]=2)[CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15]

Participants

5

Reactant 3

HCID 673313,6-DichloropyridazineHCID 81531DiisopropylethylamineHCID 59130986methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate2×

Product 1

HCID 59808482Methyl(3S,4R)-4-(2,4-difluorophenyl)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The product of Step A, methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate (0.46 g, 1.91 mmol) was dissolved in dioxane (2 ml). DIPEA (1.33 mL, 7.64 mmol) and 3,6-dichloropyridazine (1.42 g, 9.55 mmol) were added. The reaction was conducted at 120° C. for 5 minutes and at 150° C. for 10 minutes with microwave. Then, the reaction mixture was concentrated in vacuo. The obtained residue was diluted with EtOAc, washed with water and purified by column chromatography (eluent: EtOAc/Hex=1/5) to give the title compound (0.44 g, 65%).

Workup

  1. concentrationThen, the reaction mixture was concentrated in vacuo
  2. additionThe obtained residue was diluted with EtOAc
  3. washwashed with water
  4. custompurified by column chromatography (eluent: EtOAc/Hex=1/5)

Sources & evidence

ORD record
ord-bc9baf6db89344b7a3e6cef72635d372
Source dataset
uspto-grants-2012_08
Patent number
US08236955B2

Reaction notes

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