Cesium carbonate → Methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate

HRID 340508

反応式

HRID 340508 の反応式
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=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.[NH2:60][C:61]1[N:70]=[C:69]([NH:71][C@@H:72]2[CH2:77][CH2:76][CH2:75][CH2:74][C@@H:73]2[NH:78][C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])[C:68]([F:86])=[CH:67][C:62]=1[C:63]([O:65][CH3:66])=[O:64]>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>[C:82]([O:81][C:79]([NH:78][C@H:73]1[CH2:74][CH2:75][CH2:76][CH2:77][C@H:72]1[NH:71][C:69]1[C:68]([F:86])=[CH:67][C:62]([C:63]([O:65][CH3:66])=[O:64])=[C:61]([NH:60][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[N:4][CH:3]=2)[N:70]=1)=[O:80])([CH3:85])([CH3:83])[CH3:84]

参加物

9

反応物 4

HCID 10796Cesium carbonateHCID 737434-BromoisoquinolineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86683887Methyl2-amino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoronicotinate

生成物 1

HCID 86683886Methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate収率 72.2%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

4-bromoisoquinoline (65 mg), cesium carbonate (170 mg), Pd2(dba)3 (29 mg), and Xantphos (36 mg) were added to a 1,4-dioxane (2.1 ml) solution containing methyl 2-amino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoronicotinate (80 mg), followed by stirring at 100° C. for 3 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, and 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 1:2), diisopropylether was added, solid matter was collected by filtration, and a light yellow solid of methyl 6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)-5-fluoro-2-(isoquinoline 4-ylamino)nicotinate (77 mg) was obtained.

後処理

  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 1:2), diisopropylether
  9. additionwas added
  10. filtrationsolid matter was collected by filtration

出典と根拠

ORDレコード
ord-4f5dfba8290e4dcb8ff5b6ab69298b73
出典データセット
uspto-grants-2014_11
特許番号
US08895585B2

関連ノート

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