Binap, (A+-)- → Tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 384644Notes

Reaction equation

HRID 384644 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:47][C:48]1[CH:53]=[N:52][C:51]([C:54]#[C:55][CH2:56][O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])=[CH:50][N:49]=1.Cl[C:66]1[N:71]=[CH:70][N:69]=[C:68]([NH:72][CH2:73][CH:74]2[CH2:79][CH2:78][N:77]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[CH2:76][CH2:75]2)[CH:67]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Si:58]([O:57][CH2:56][C:55]#[C:54][C:51]1[N:52]=[CH:53][C:48]([NH:47][C:66]2[N:71]=[CH:70][N:69]=[C:68]([NH:72][CH2:73][CH:74]3[CH2:75][CH2:76][N:77]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[CH2:78][CH2:79]3)[CH:67]=2)=[N:49][CH:50]=1)([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:59])[CH3:60]

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 45787122tert-Butyl 4-(((6-chloropyrimidin-4-yl)amino)methyl)piperidine-1-carboxylateHCID 59613433HCID 59613433, compound

Product 1

HCID 66746379Tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
145 °C

Procedure

2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (56 mg, 0.09 mmol) and palladium acetate (4 mg, 0.015 mmol) were suspended in 5 mL toluene (5 mL) and degassed over 10 minutes under a stream of nitrogen gas. 2-Amino-5-(3-(tert-butyldimethyl-silyloxy)prop-1-ynyl)pyrazine (50 mg, 0.15 mmol) and tert-butyl 4-((6-chloropyrimidin-4-ylamino)methyl)-piperidine-1-carboxylate (40 mg, 0.15 mmol), in anhydrous and degassed DMF (500 μL), and sodium tert-butoxide (46 mg, 0.45 mmol) were added and the reaction mixture was heated at 145° C. for 30 minutes by microwave irradiation. The mixture was evaporated to dryness. The residue was partitioned between water and dichloromethane and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated. The residue was redissolved in methanol and filtered through a PS-SH column. The filtrate was evaporated to dryness to give crude tert-butyl 4-((6-(5-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)pyrazin-2-yl-amino)pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate which was used directly for the next step.

Workup

  1. customdegassed over 10 minutes under a stream of nitrogen gas
  2. additionwere added
  3. customThe mixture was evaporated to dryness
  4. customThe residue was partitioned between water and dichloromethane
  5. extractionthe aqueous phase was extracted with dichloromethane
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in methanol
  9. filtrationfiltered through a PS-SH column
  10. customThe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-42f14f1aa7cd49d6bff836eda41479b0
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

Loading…