Cesium carbonate → Tert-butyl cis-2-(6-(5-methylpyridin-3-ylamino)-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

HRID 340506

반응식

HRID 340506 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Cl[C:58]1[N:63]=[C:62]([NH:64][C@H:65]2[CH2:70][CH2:69][CH2:68][CH2:67][C@H:66]2[NH:71][C:72](=[O:78])[O:73][C:74]([CH3:77])([CH3:76])[CH3:75])[C:61]([F:79])=[CH:60][C:59]=1[C:80]#[N:81]>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].C(OCC)(=O)C.O.O1CCOCC1>[CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:58]2[N:63]=[C:62]([NH:64][C@H:65]3[CH2:70][CH2:69][CH2:68][CH2:67][C@H:66]3[NH:71][C:72](=[O:78])[O:73][C:74]([CH3:76])([CH3:77])[CH3:75])[C:61]([F:79])=[CH:60][C:59]=2[C:80]#[N:81])[CH:5]=[N:6][CH:7]=1

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27628943-Amino-5-methylpyridineHCID 86683848Tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

생성물 1

HCID 86683885Tert-butyl cis-2-(6-(5-methylpyridin-3-ylamino)-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate수율 87.6%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

5-methyl-3-pyridineamine (191 mg), cesium carbonate (1.10 g), Pd2(dba)3 (186 mg), and Xantphos (235 mg) were added to a 1,4-dioxane (14 ml) solution containing tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (500 mg), followed by stirring at 100° C. for 2 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. Insoluble matter was removed by filtration, the filter cake was washed with water and ethyl acetate, the organic layer was collected, washed with saturated saline, and dried over anhydrous magnesium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 1:4), diisopropylether was added, solid matter was collected by filtration, and a light yellow solid of tert-butyl cis-2-(6-(5-methylpyridin-3-ylamino)-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (523 mg) was thus obtained.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customInsoluble matter was removed by filtration
  3. washthe filter cake was washed with water and ethyl acetate
  4. customthe organic layer was collected
  5. washwashed with saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled away under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 1:4), diisopropylether
  9. additionwas added
  10. filtrationsolid matter was collected by filtration

출처 및 근거

ORD 기록
ord-983d100231444fbfb0191e96303b33e1
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895585B2

연결된 노트

불러오는 중…