Cesium carbonate → tert-butyl 1-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperidin-4-ylcarbamate

HRID 79412노트

반응식

HRID 79412 반응식
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][N:14]2[C:22]3[C:17](=[C:18]([NH:23][C:24]([C:26]4[N:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]5=[N:28][CH:27]=4)=[O:25])[CH:19]=[CH:20][CH:21]=3)[C:16]([CH2:35][CH3:36])=[N:15]2)[N:8]=1)(=O)=O.[NH:39]1[CH2:44][CH2:43][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:41][CH2:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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].C1(C)C=CC=CC=1>[CH2:35]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][C:18]=2[NH:23][C:24]([C:26]2[N:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]3=[N:28][CH:27]=2)=[O:25])[N:14]([CH2:13][C:9]2[N:8]=[C:7]([N:39]3[CH2:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:43][CH2:44]3)[CH:12]=[CH:11][CH:10]=2)[N:15]=1)[CH3:36]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 7238334-(N-Boc-amino)piperidineHCID 866722116-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl trifluoromethanesulfonate

생성물 1

HCID 67262218tert-butyl 1-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperidin-4-ylcarbamate수율 44.6%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

To a reaction vial was added 6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl trifluoromethanesulfonate (30 mg, 0.0551 mmol; prepared according to Example 24, Step A), tert-butyl piperidin-4-ylcarbamate (22.1 mg, 0.110 mmol) and cesium carbonate (53.9 mg, 0.165 mmol). Toluene (2 mL) was added and argon was bubbled through the mixture for 10 minutes. To this mixture was added rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.86 mg, 0.0110 mmol) and tris(dibenzylideneacetonyl)bis-palladium (5.05 mg, 0.00551 mmol). The reaction mixture was heated at 90° C. for 4 hours. The mixture was filtered through Celite®, washing with dichloromethane and methanol. The solution was concentrated under a stream of nitrogen and the residue was purified by preparative thin layer chromatography on silica, eluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution to give tert-butyl 1-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperidin-4-ylcarbamate (14.6 mg).

후처리

  1. customargon was bubbled through the mixture for 10 minutes
  2. filtrationThe mixture was filtered through Celite®
  3. washwashing with dichloromethane and methanol
  4. concentrationThe solution was concentrated under a stream of nitrogen
  5. customthe residue was purified by preparative thin layer chromatography on silica
  6. washeluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution

출처 및 근거

ORD 기록
ord-b2df757e4e2e4aa6931f2e4ca9659b23
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841455B2

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