Binap, (A+-)- → 4-chloro-6-(2,3-difluoro-benzylamino)-2H-phthalazin-1-one

HRID 1667474Notes

Reaction equation

HRID 1667474 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].[F:14][C:15]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH2:18].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:18][CH2:17][C:16]3[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:15]=3[F:14])[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27369412,3-DifluorobenzylamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 249485324-chloro-6-(2,3-difluoro-benzylamino)-2H-phthalazin-1-oneYield 14%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (156 mg, 0.601 mmol), 2,3-difluorobenzylamine (0.074 mL, 0.646 mmol), Pd2(dba)3 (53 mg, 0.058 mmol), rac-BINAP (104 mg, 0.167 mmol) and NaOtBu (134 mg, 1.39 mmol) in DMA (6 mL) was heated at 80° C. for 1.5 h. 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-(2,3-difluoro-benzylamino)-2H-phthalazin-1-one (27 mg) as an off white solid, 1H (400 MHz, CDCl3) δ: 4.45 (s, 2H), 6.84 (d, 1H), 6.96 (m, 2H), 7.03 (m, 2H), 8.01 (d, 1H), 11.00 (s, 1H) ppm; m/z (M+1) 321.91.

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-661dc6ab85564772a9398df3ccf29a14
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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