Potassium Phosphate, Tribasic → (R)-4-(4-(4-benzoyl-2-methylpiperazin-1-yl)phthalazin-1-yl)benzamide

HRID 1689974Notes

Reaction equation

HRID 1689974 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]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[O:19])[CH2:14][C@H:13]2[CH3:26])=[N:4][N:3]=1.[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])[NH2:28].C1(P(C2CCCCC2)C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[C:18]([N:15]1[CH2:16][CH2:17][N:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([C:33]3[CH:34]=[CH:35][C:30]([C:27]([NH2:28])=[O:29])=[CH:31][CH:32]=3)=[N:3][N:4]=2)[C@H:13]([CH3:26])[CH2:14]1)(=[O:19])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27378114-Aminocarbonylphenylboronic acidHCID 57474835Dicyclohexyl(2,6-dimethoxyphenyl)phosphineHCID 57581516(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(cyclohexyl)methanone

Product 1

HCID 49862220(R)-4-(4-(4-benzoyl-2-methylpiperazin-1-yl)phthalazin-1-yl)benzamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

Compound 71 was prepared according to general method H. A 15 mL Schlenk tube was charged with (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(cyclohexyl)methanone JK-5 (130 mg, 349 μmol), 4-carbamoylphenylboronic acid (77 mg, 523 μmol), tris(dibenzylideneacetone)dipalladium (0) (3.2 mg, 3.5 μmol), dicyclohexyl(2,6-dimethoxyphenyl)phosphine (2.3 mg, 7.0 μmol), and potassium phosphate tribasic (148 mg, 697 μmol). The vessel was evacuated, backfilled with argon 5 times, and then previously degassed n-butanol (1 mL) was added. The reaction was heated at 100° C. for 20 hours. After cooling, the reaction was added to aqueous K2CO3 (10%) and extracted three times with dichloromethane. The combined 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 71. MS (M+H)+=452.2.

Workup

  1. customCompound 71 was prepared
  2. customThe vessel was evacuated
  3. additionpreviously degassed n-butanol (1 mL) was added
  4. temperatureAfter cooling
  5. additionthe reaction was added to aqueous K2CO3 (10%)
  6. extractionextracted three times with dichloromethane
  7. dry with materialThe combined organics were dried (MgSO4)
  8. customevaporated
  9. customto give a yellow oil

Sources & evidence

ORD record
ord-4afedb6ebee045749f1a752944c8deea
Source dataset
uspto-grants-2012_04
Patent number
US08153633B2

Reaction notes

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