Binap, (A+-)- → 4-{2-[(4-Chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-4-trifluoromethyl-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1803619Notes

Reaction equation

HRID 1803619 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[Cl:13].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=2[CH2:37][NH2:38])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>CC(N(C)C)=O.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:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:29][C:28]=2[CH2:37][NH:38][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[NH:7][N:6]=[C:5]3[Cl:13])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 674164364-(2-Aminomethyl-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 674154924-{2-[(4-Chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-4-trifluoromethyl-phenyl}-piperazine-1-carboxylic acid tert-butyl esterYield 7.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-bromo-4-chloro-2H-phthalazin-1-one (183 mg, 0.70 mmol), 4-(2-aminomethyl-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (230 mg, 0.64 mmol), Pd2(dba)3 (59 mg, 0.064 mmol), BINAP (120 mg, 0.19 mmol) and NaOt-Bu (180 mg, 1.92 mmol) in DMA (10 mL) was purged with nitrogen for 10 min. The mixture was heated at 90° C. for 5 h. The mixture was allowed to cool and diluted with ethyl acetate (30 mL) and washed with ammonium chloride (25 mL). The organic layer was dried and concentrated. Chromatography on silica yielded the title compound (25 mg) m/z (M+H)=538.90.

Workup

  1. customwas purged with nitrogen for 10 min
  2. temperatureto cool
  3. additiondiluted with ethyl acetate (30 mL)
  4. washwashed with ammonium chloride (25 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9917671f29b9469b8226ec7b30c9bea2
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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