Binap, (A+-)- → HCID 67417840, compound

HRID 1667448Notes

Reaction equation

HRID 1667448 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][CH:30]=[CH:29][C:28]=2[CH2:33][NH2:34])[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.CCOC(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[CH2:22][CH2:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH2:33][NH:34][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])[CH2:25][CH2:26]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 4961274Tert-butyl 4-[2-(aminomethyl)phenyl]piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 67417840HCID 67417840, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.58 mmol), 4-(2-aminomethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (187 mg, 0.64 mmol), Pd2(dba)3 (53 mg, 0.058 mmol), rac-BINAP (132 mg, 0.17 mmol) and NaOt-Bu (140 mg, 1.45 mmol) in DMA (6 mL) was heated at 80° C. for 1 h. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) yielded 4-{2-[(4-chloro-1-oxo-1,2-dihydro-phthalazin-6-ylamino)-methyl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester. Deprotection with TFA in DCM yielded the title compound. 4-Chloro-6-(2-piperazin-1-yl-benzylamino)-2H-phthalazin-1-one: 46 mg (16.9%): m/z (M+H)=370.00. 1H-NMR (DMSO-d6) δ: 12.31 (s, 1H), 7.89 (d, 1H), 7.77 (m, 1H), 7.33 (d, 1H), 7.21 (m, 1H), 7.14 (dd, 1H), 7.10 (m, 1H), 7.00 (m, 1H), 6.64 (s, 1H), 4.43 (d, 2H), 2.90 (m, 5H), 2.82 (m, 4H).

Workup

  1. temperatureto cool
  2. washwashed with water (25 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0a82dbec61c544f88864db4fbd2aa055
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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