Toluene → 3-(4-fluoro-phenyl)-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine

HRID 1479945Notes

Reaction equation

HRID 1479945 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([N:10]2[CH2:15][CH2:14][NH:13][C@H:12]([CH3:16])[CH2:11]2)=[C:6]([CH3:9])[C:7]=1[CH3:8].[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C1(C)C=CC=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:2]2[N:3]=[N:4][C:5]([N:10]3[CH2:15][CH2:14][NH:13][C@H:12]([CH3:16])[CH2:11]3)=[C:6]([CH3:9])[C:7]=2[CH3:8])=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 2856454-Fluorophenylboronic acidHCID 591915183-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine

Product 1

HCID 591915663-(4-fluoro-phenyl)-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazineYield 83%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a round bottom flask is added 3-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine (500 mg, 2.07 mmol), 4-fluorophenylboronic acid (580 mg, 4.15 mmol) sodium carbonate (440 mg, 4.15 mmol), toluene (16 mL) and water (8 mL). The reaction mixture is purged with nitrogen for 20 min. Tetrakis(triphenylphosphine) palladium (50 mg, 0.103 mmol) is added and the mixture is heated to 110° C. for 18 h. The reaction mixture is concentrated and partitioned between ethylacetate and water. It is extracted with ethylacetate twice and the combined organic phases are dried with sodium sulfate and concentrated. It is purified by column chromatography (0-25% methanol/methylene chloride) to give 480 mg of 3-(4-fluoro-phenyl)-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine (83%).

Workup

  1. customThe reaction mixture is purged with nitrogen for 20 min
  2. concentrationThe reaction mixture is concentrated
  3. custompartitioned between ethylacetate and water
  4. extractionIt is extracted with ethylacetate twice
  5. dry with materialthe combined organic phases are dried with sodium sulfate
  6. concentrationconcentrated
  7. customIt is purified by column chromatography (0-25% methanol/methylene chloride)

Sources & evidence

ORD record
ord-67a1f7431eb9495cb8e2f3ccc9a73f93
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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