Binap, (A+-)- → 4-chloro-6-(2-morpholin-4-yl-benzylamino)-4a,8a-dihydro-2H-phthalazin-1-one

HRID 1667524Notes

Reaction equation

HRID 1667524 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].[O:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=2[CH2:22][NH2:23])[CH2:16][CH2:15]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[CH:4]2[CH:9]([CH:10]=[CH:11][C:2]([NH:23][CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=3[N:17]3[CH2:18][CH2:19][O:14][CH2:15][CH2:16]3)=[CH:3]2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 2776563(2-(Morpholin-4-yl)phenyl)methanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 674442344-chloro-6-(2-morpholin-4-yl-benzylamino)-4a,8a-dihydro-2H-phthalazin-1-oneYield 10.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (1.227 g, 4.728 mmol), (2-morpholino)benzylamine (1.00 g, 5.201 mmol), Pd2(dba)3 (450 mg, 0.491 mmol), rac-BINAP (883 mg, 1.418 mmol) and NaOtBu (1.17 g, 12.175 mmol) in DMA (20 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 (Hexanes/EtOAc) afforded 4-chloro-6-(2-morpholin-4-yl-benzylamino)-4a,8a-dihydro-2H-phthalazin-1-one (180 mg) as a white solid. 1H (400 MHz, d6-DMSO) δ: 2.90 (m, 4H), 3.79 (m, 4H), 4.46 (d, 2H), 6.66 (bs, 1H), 7.04 (t, 1H), 7.15 (m, 2H), 7.24 (m, 1H), 7.35 (d, 1H), 7.77 (t, 1H), 7.90 (d, 1H), 12.32 (s, 1H) ppm; m/z (M+1) 371.23.

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-144acc7362614f6cb7cd14dabe2b6103
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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