Binap, (A+-)- → 4-chloro-6-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-2H-phthalazin-1-one

HRID 1667492Notes

Reaction equation

HRID 1667492 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[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]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]([N:23]3[CH2:24][CH2:25][N:20]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][N:14]=4)[CH2:21][CH2:22]3)[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27346391-PiperazinylpyrazineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 249470354-chloro-6-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-2H-phthalazin-1-oneYield 16.7%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (145 mg, 0.559 mmol), 1-(2-pyrazinyl)piperazine (104 mg, 0.633 mmol), Pd2(dba)3 (43 mg, 0.047 mmol), rac-BINAP (116 mg, 0.186 mmol) and NaOtBu (167 mg, 1.738 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). Preparatory HPLC afforded 4-chloro-6-(2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-2H-phthalazin-1-one (32 mg) as a yellow solid, 1H (400 MHz, d6-DMSO) δ: 3.62 (m, 4H), 3.78 (m, 4H), 7.12 (d, 1H), 7.60 (dd, 1H), 7.87 (d, 1H), 8.07 (d, 1H), 8.11 (m, 1H), 8.37 (s, 1H), 12.51 (s, 1H) ppm. m/z (M+1) 342.98.

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-f67a6f891ef740a7aae88db4dddbf12e
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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