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 384644노트

반응식

HRID 384644 반응식
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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 6228Dimethylformamide용매

반응 조건

온도
145 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-42f14f1aa7cd49d6bff836eda41479b0
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367658B2

반응 노트

불러오는 중…