Morpholine → (R)-(3-methyl-4-(4-morpholinophthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

HRID 1689971Notes

Reaction equation

HRID 1689971 reaction equation
CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1.Cl[C:54]1[C:63]2[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=2)[C:57]([N:64]2[CH2:69][CH2:68][N:67]([C:70]([C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)=[O:71])[CH2:66][C@H:65]2[CH3:78])=[N:56][N:55]=1.[NH:79]1[CH2:84][CH2:83][O:82][CH2:81][CH2:80]1>ClCCl.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]>[CH3:78][C@H:65]1[N:64]([C:57]2[C:58]3[C:63](=[CH:62][CH:61]=[CH:60][CH:59]=3)[C:54]([N:79]3[CH2:84][CH2:83][O:82][CH2:81][CH2:80]3)=[N:55][N:56]=2)[CH2:69][CH2:68][N:67]([C:70]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)=[O:71])[CH2:66]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 57581487(R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanoneHCID 86595863(+/-)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl

Product 1

HCID 66904757(R)-(3-methyl-4-(4-morpholinophthalazin-1-yl)piperazin-1-yl)(phenyl)methanone

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Compound 66 was prepared as described in general method E. Sodium t-butoxide (0.0550 g, 0.572 mmol), rac-2,2-bis(diphenylphosphino)-1,1-binaphthalene (0.0102 g, 0.0164 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.00749 g, 0.00818 mmol), and (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone JK-5 (0.150 g, 0.409 mmol) were combined in a screw cap vial, purged to argon, and solvated with degassed morpholine (0.142 mL, 1.64 mmol). The reaction vial was sealed and stirred at 80° C. After 16 h, the reaction was taken up in dichloromethane and directly loaded onto silica gel. Purification by column chromatography (gradient elution 40 to 100% ethyl acetate in hexanes) afforded 66. MS (M+H)+=418.1.

Workup

  1. customCompound 66 was prepared
  2. customcap vial
  3. custompurged to argon
  4. customThe reaction
  5. customvial was sealed
  6. customPurification
  7. washby column chromatography (gradient elution 40 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fe40f602191d402fafc846fd49d0d13a
Source dataset
uspto-grants-2012_04
Patent number
US08153633B2

Reaction notes

Loading…