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

HRID 1667490Notes

Reaction equation

HRID 1667490 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]([CH2:20][C:21]2[CH:22]=[C:23]([CH2:27][NH2:28])[CH:24]=[CH:25][CH:26]=2)[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[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:28][CH2:27][C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([CH2:20][N:17]4[CH2:18][CH2:19][O:14][CH2:15][CH2:16]4)[CH:22]=3)[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 64841823-Morpholin-4-ylmethyl-benzylamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 584472674-chloro-6-(3-morpholin-4-ylmethyl-benzylamino)-2H-phthalazin-1-oneYield 18.9%

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), [3-(morpholinomethyl)phenyl]methylamine (131 mg, 0.636 mmol), Pd2(dba)3 (53 mg, 0.0578 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 1 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-(3-morpholin-4-ylmethyl-benzylamino)-2H-phthalazin-1-one (42 mg) as an off white solid, 1H (400 MHz, d6-DMSO) δ: 2.11 (m, 4H), 3.23 (s, 2H), 3.30 (t, 4H), 4.25 (d, 2H), 6.60 (s, 1H), 6.98 (m, 2H), 7.10 (m, 3H), 7.50 (t, 1H), 7.74 (d, 1H), 12.16 (s, 1H) ppm; m/z (M+1) 384.94.

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-179d73da657d4941aad0ae4eb85fae11
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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