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

HRID 1667540Notes

Reaction equation

HRID 1667540 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].BrC1C=C2C(C(Cl)=NNC2=O)=CC=1.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=2[CH2:48][NH2:49])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].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:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][C:41]=2[CH2:48][NH:49][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])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

Participants

8

Reactant 5

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 674169997-bromo-4-chloro-2H-phthalazin-1-oneHCID 674174384-(2-Aminomethyl-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 674170634-(2-[(4-Chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl esterYield 18%

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 and 7-bromo-4-chloro-2H-phthalazin-1-one (300 mg, 1.16 mmol), 4-(2-aminomethyl-4-methoxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (338 mg, 1.05 mmol), Pd2(dba)3 (110 mg, 0.12 mmol), BINAP (217 mg, 0.35 mmol) and NaOt-Bu (327 mg, 3.48 mmol) in DMA (10 mL) was purged with nitrogen for 10 min. The mixture was heated at 90° C. for 1.5 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 (102 mg, 18%) m/z (M+H)=500.32.

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-832102e8b3a54426bfb0a9ff0508e0f6
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

Loading…