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

HRID 1803570Notes

Reaction equation

HRID 1803570 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]([F:26])([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][C:15]([F:14])([F:25])[F:26])[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 2777251(2-(Trifluoromethoxy)phenyl)methanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 584473164-chloro-6-(2-trifluoromethoxy-benzylamino)-2H-phthalazin-1-oneYield 19.2%

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-(trifluoromethoxy)benzylamine (122 mg, 0.636 mmol), Pd2(dba)3 (49 mg, 0.0535 mmol), rac-BINAP (104 mg, 0.167 mmol) and NaOtBu (142 mg, 1.478 mmol) in DMA (5 mL) was heated at 85° 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-trifluoromethoxy-benzylamino)-2H-phthalazin-1-one (41 mg) as a beige solid, 1H (400 MHz, d6-DMSO) δ: 4.50 (s, 2H), 6.78 (s, 1H), 7.16 (dd, 1H), 7.40 (m, 3H), 7.47 (d, 1H), 7.68 (t, 1H)m 7.95 (d, 1H), 12.37 (s, 1H) ppm; m/z (M+1) 369.86.

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-c03f790ed0ac42a9b3f097942d8810e7
Source dataset
uspto-grants-2013_01
Patent number
US08349836B2

Reaction notes

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