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

HRID 1803571Notes

Reaction equation

HRID 1803571 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][CH:15]([F:25])[O:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].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:20][CH2:19][C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=3[O:16][CH:15]([F:14])[F:25])[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 15140621-[2-(Difluoromethoxy)phenyl]methanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 584473404-chloro-6-(2-difluoromethoxy-benzylamino)-2H-phthalazin-1-oneYield 6.9%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.578 mmol), 2-(difluoromethoxy)benzylamine (110 mg, 0.636 mmol), Pd2(dba)3 (47 mg, 0.051 mmol), rac-BINAP (108 mg, 0.173 mmol) and NaOtBu (139 mg, 1.445 mmol) in DMA (5 mL) was heated at 85° C. for 2 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-difluoromethoxy-benzylamino)-2H-phthalazin-1-one (14 mg) as a yellow solid, 1H (400 MHz, d6-DMSO) δ: 4.43 (d, 2H), 6.81 (s, 1H), 7.14 (dd, 1H), 7.22 (m, 2H), 7.27 (t, 1H), 7.37 (m, 2H), 7.60 (t, 1H), 7.93 (d, 1H), 12.35 (s, 1H) ppm; m/z (M+1) 351.92.

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-1db472a15e0a4ade94cf211fa99696fc
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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