Toluene → (R)-(3-methyl-4-(4-p-tolylphthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

HRID 1689970Notes

Reaction equation

HRID 1689970 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:19])[CH2:14][C@H:13]2[CH3:26])=[N:4][N:3]=1.[C:27]1([CH3:36])[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:26][C@H:13]1[N:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([C:30]3[CH:31]=[CH:32][C:27]([CH3:36])=[CH:28][CH:29]=3)=[N:3][N:4]=2)[CH2:17][CH2:16][N:15]([C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:19])[CH2:14]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 57581487(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone

Product 1

HCID 46891200(R)-(3-methyl-4-(4-p-tolylphthalazin-1-yl)piperazin-1-yl)(phenyl)methanoneYield 86.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Compound 20 was prepared as described generally in synthetic Method D. Substrate JK-5 was prepared as described in detail in Example 11. To a reaction flask was added (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone (JK-5) (200 mg, 0.54 mmol), p-tolyl boronic acid (111 mg, 0.82 mmol, 1.5 eq), and Pd(PPh3)4 (31 mg, 0.027 mmol, 0.05 eq). The flask was fitted with a reflux condenser and purged with nitrogen. Toluene (5.4 mL) and aqueous Na2CO3 (2 M, 0.54 mL, 2 eq) were added and the reaction was heated to 100° C. overnight. The reaction was then cooled to rt and diluted with 75 mL of ethyl acetate. The organic phase was washed with 1×10 mL of sat. NaHCO3 solution, 1×10 mL of H2O, and 1×10 mL of sat. NaCl solution. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography (60% ethyl acetate in hexanes) afforded 197 mg (86%) of (R)-(3-methyl-4-(4-p-tolylphthalazin-1-yl)piperazin-1-yl)(phenyl)methanone 20 MS (M+H)+=423.3.

Workup

  1. customCompound 20 was prepared
  2. customwas prepared
  3. customThe flask was fitted with a reflux condenser
  4. custompurged with nitrogen
  5. temperatureThe reaction was then cooled to rt
  6. washThe organic phase was washed with 1×10 mL of sat. NaHCO3 solution, 1×10 mL of H2O, and 1×10 mL of sat. NaCl solution
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography (60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a866e661464a47339d863ba3673e4977
Source dataset
uspto-grants-2012_04
Patent number
US08153633B2

Reaction notes

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