Binap, (A+-)- → 4-Chloro-6-[2-(4-methyl-piperazin-1-yl)-benzylamino]-2H-phthalazin-1-one

HRID 1667444Notes

Reaction equation

HRID 1667444 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].[CH3:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=2[CH2:23][NH2:24])[CH2:17][CH2:16]1.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]>[Cl:13][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:24][CH2:23][C:22]3[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=3[N:18]3[CH2:17][CH2:16][N:15]([CH3:14])[CH2:20][CH2:19]3)[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27955682-(4-Methyl-1-piperazinyl)benzenemethanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 249463384-Chloro-6-[2-(4-methyl-piperazin-1-yl)-benzylamino]-2H-phthalazin-1-one

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), 2-(4-methyl-piperazin-1-yl)-benzylamine (132 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 the title compound. 4-Chloro-6-[2-(4-methyl-piperazin-1-yl)-benzylamino]-2H-phthalazin-1-one: 46 mg (20.7%): m/z (M+H)=384. 1H-NMR (DMSO-d6) δ: 12.31 (s, 1H), 7.89 (d, 1H), 7.77 (m, 1H), 7.33 (dd, 1H), 7.20 (m, 1H), 7.13 (m, 2H), 7.00 (m, 1H), 6.63 (s, 1H), 4.42 (d, 2H), 2.98 (m, 4H), 2.52 (m, 4H), 2.23 (s, 3H).

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-5ca1677eb7ec4adfaada18f4a2b91663
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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