Binap, (A+-)- → HCID 58447288, compound

HRID 1667521Notes

Reaction equation

HRID 1667521 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([CH2:19][C:20]2[CH:21]=[C:22]([CH2:26][NH2:27])[CH:23]=[CH:24][CH:25]=2)[CH2:18][CH2:17][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:27][CH2:26][C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([CH2:19][N:14]4[CH2:18][CH2:17][CH2:16][CH2:15]4)[CH:21]=3)[CH:3]=2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 47124781-{3-[(Pyrrolidin-1-yl)methyl]phenyl}methanamineHCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-one

Product 1

HCID 58447288HCID 58447288, compoundYield 5.3%

Reagents, catalysts & solvents 3

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

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (200 mg, 0.770 mmol), [3-(1-pyrrolidinylmethyl)phenyl]methanamine (161 mg, 0.848 mmol), Pd2(dba)3 (71 mg, 0.077 mmol), rac-BINAP (144 mg, 0.231 mmol) and NaOtBu (230 mg, 2.393 mmol) in DMA (6 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 (Hexanes/EtOAc) afforded 4-chloro-6-(3-pyrrolidin-1-ylmethyl-benzylamino)-2H-phthalazin-1-one (15 mg) as a yellow solid. 1H (400 MHz, d6-DMSO) δ: 1.62 (m, 4H), 2.38 (m, 4H), 3.55 (m, 2H), 4.44 (d, 2H), 6.80 (s, 1H), 7.17 (m, 2H), 7.3 (m, 3H), 7.68 (m, 1H), 7.92 (d, 1H), 12.34 (s, 1H) ppm; m/z (M+1) 369.26.

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-1057cc0bb0794526ac231ce60fe4f00b
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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