Binap, (A+-)- → 4-chloro-6-(2-imidazol-1-yl-benzylamino)-2H-phthalazin-1-one

HRID 1803572Notes

Reaction equation

HRID 1803572 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].[N:14]1([C:19]2[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=2[CH2:21][NH2:22])[CH:18]=[CH:17][N:16]=[CH:15]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:22][CH2:21][C:20]3[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=3[N:14]3[CH:18]=[CH:17][N:16]=[CH:15]3)[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 31616711-[2-(1H-imidazol-1-yl)phenyl]methanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 249483384-chloro-6-(2-imidazol-1-yl-benzylamino)-2H-phthalazin-1-oneYield 8.5%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (148 mg, 0.570 mmol), 2-imidazol-1-yl-benzylamine (110 mg, 0.635 mmol), Pd2(dba)3 (53 mg, 0.0578 mmol), rac-BINAP (117 mg, 0.188 mmol) and NaOtBu (227 mg, 2.362 mmol) in DMA (5 mL) was heated at 85° C. for 45 minutes. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Chromatography on silica (EtOAc/hexanes) afforded 4-chloro-6-(2-imidazol-1-yl-benzylamino)-2H-phthalazin-1-one (17 mg) as a yellow solid, 1H (400 MHz, d6-DMSO) δ: 4.24 (d, 2H), 6.64 (s, 1H), 7.06 (dd, 1H), 7.11 (s, 1H), 7.41 (m, 1H), 7.46 (m, 2H), 7.52 (m, 2H), 7.59 (t, 1H), 7.92 (m, 2H), 12.36 (1H) ppm; m/z (M+1) 351.99.

Workup

  1. temperatureto cool
  2. washwashed with water
  3. washThe organic layer was washed with sat.aq
  4. dry with materialNaHCO3, brine and dried (Na2SO4)

Sources & evidence

ORD record
ord-25b2b84116254cb7b3dfb7ccdf69300c
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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