Sodium Carbonate → ((R)-3-methyl-4-(4-(4-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)phenyl)phthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

HRID 1689980Notes

Reaction equation

HRID 1689980 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.[O:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]1[O:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[CH3:26][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:39]3[CH:40]=[CH:41][C:36]([CH2:35][CH2:34][O:33][CH:28]4[CH2:29][CH2:30][CH2:31][CH2:32][O:27]4)=[CH:37][CH:38]=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 3

HCID 10340Sodium CarbonateHCID 44890903(4-(2-((Tetrahydro-2H-pyran-2-yl)oxy)ethyl)phenyl)boronic acidHCID 57581487(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone

Product 1

HCID 57581517((R)-3-methyl-4-(4-(4-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)phenyl)phthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone (JK-5) (200 mg, 0.545 mmol), 4-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)phenylboronic acid (136 mg, 0.545 mmol) and tetrakis(triphenylphosphine)palladium (0) (31.5 mg, 0.0273 mmol) were dissolved in toluene (4 mL) and aqueous sodium carbonate (2.0M, 0.400 mL) under an atmosphere of argon. The reaction was heated at 100° C. for 15 hours, cooled to rt, and taken up in ethyl acetate (80 mL). After washing with aqueous K2CO3 (10%), water, and saturated sodium chloride, the organics were dried (MgSO4) and evaporated to give a yellow oil. Chromatography over silica gel with a gradient of hexanes/0-100% ethyl acetate gave a pale yellow solid, compound 83. MS (M+H)+=537.4.

Workup

  1. temperaturecooled to rt
  2. washAfter washing with aqueous K2CO3 (10%), water, and saturated sodium chloride
  3. dry with materialthe organics were dried (MgSO4)
  4. customevaporated
  5. customto give a yellow oil

Sources & evidence

ORD record
ord-3c1c5f9389d44beb9673948826da1446
Source dataset
uspto-grants-2012_04
Patent number
US08153633B2

Reaction notes

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