Binap, (A+-)- → HCID 67418200, compound

HRID 1667529Notes

Reaction equation

HRID 1667529 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].[CH3:14][C@H:15]1[NH:20][CH2:19][CH2:18][N:17]([C:21]2[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=2[CH2:23][NH2:24])[CH2:16]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.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:24][CH2:23][C:22]3[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=3[N:17]3[CH2:18][CH2:19][NH:20][C@H:15]([CH3:14])[CH2:16]3)=[CH:3]2)[C:8](=[O:12])[NH:7][N:6]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 533084876-Bromo-4-chlorophthalazin-1(2H)-oneHCID 67416422HCID 67416422, compound

Product 1

HCID 67418200HCID 67418200, compoundYield 12.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Procedure

A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (670 mg, 2.582 mmol), 2-((R)-3-methyl-piperazin-1-yl)-benzylamine (542 mg, 2.693 mmol), Pd2(dba)3 (246 mg, 0.269 mmol), rac-BINAP (505 mg, 0.811 mmol) and NaOtBu (774 mg, 8.054 mmol) in DMA (13 mL) was heated at 80° C. for 2 h. The mixture was allowed to cool, filtered through celite and rinsed with EtOAc (this layer was discarded), then MeOH. The MeOH filtrate was concentrated followed by column chromatography (EtOAc/MeOH+0.1% NH4OH) afforded 4-chloro-6-[2-((R)-3-methyl-piperazin-1-yl)-benzylamino]-4a,8a-dihydro-2H-phthalazin-1-one (121 mg) as a brown solid. 1H (400 MHz, d6-DMSO) δ: 1.22 (d, 3H), 2.73 (m, 1H), 2.95 (m, 1H), 3.1 (m, 5H), 4.47 (d, 2H), 6.67 (s, 1H), 7.06 (m, 1H), 7.14 (d, 2H), 7.25 (m, 1H), 7.35 (d, 1H), 7.78 (t, 1H), 7.90 (d, 1H), 12.33 (s, 1H) ppm; m/z (M+1) 384.28.

Workup

  1. temperatureto cool
  2. filtrationfiltered through celite
  3. washrinsed with EtOAc (this layer
  4. concentrationThe MeOH filtrate was concentrated

Sources & evidence

ORD record
ord-3980e393e7d8465ca34a11034b31ddb0
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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