Benzimidazole → HCID 59326866, 화합물

HRID 1880142노트

반응식

HRID 1880142 반응식
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.C(OC(C)C)(OC(C)C)OC(C)C.C([O:25][C:26]([C:28]1[CH:53]=[CH:52][C:31]([O:32][C:33]2[C:38]([CH:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)=[CH:37][CH:36]=[CH:35][N:34]=2)=[CH:30][CH:29]=1)=O)C.C([N-]C(C)C)(C)C.[Li+]>C1(C)C=CC=CC=1.C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:26]([C:28]1[CH:29]=[CH:30][C:31]([O:32][C:33]2[C:38]([CH:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:46])[CH2:43][CH2:44]3)=[CH:37][CH:36]=[CH:35][N:34]=2)=[CH:52][CH:53]=1)=[O:25]

참가 물질

7

반응물 4

HCID 5798BenzimidazoleHCID 78191Propane, 2,2',2''-[methylidynetris(oxy)]tris-HCID 2724682Lithium diisopropylamideHCID 59326865Tert-butyl 4-(2-(4-(ethoxycarbonyl)phenoxy)pyridin-3-YL)piperidine-1-carboxylate

생성물 1

HCID 59326866HCID 59326866, 화합물

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of benzimidazole (0.351 g, 2.97 mmol) and triisopropyl orthoformate (3.9 mL, 17.61 mmol) in toluene (25 mL) was heated in a 100 mL round bottom flask equipped with a Dean-Stark trap and reflux condenser under an atmosphere of nitrogen. After 1 h the solvent was removed in vacuo. The residue was dissolved in THF (8 mL) and to the solution was added a solution of tert-butyl 4-(2-(4-(ethoxycarbonyl)phenoxy)pyridin-3-yl)piperidine-1-carboxylate (1.07 g, 2.509 mmol) in THF (8 mL). The mixture was cooled (−78° C.) and lithium diisopropylamide (2.0M solution in heptane/THF/ethylbenzene, 1.80 mL, 3.60 mmol) was added dropwise resulting in a reddish solution. After 2 h the reaction was quenched with saturated NH4Cl and allowed to warm to rt. The mixture was partitioned between EtOAc/saturated NaHCO3. The organic layer was washed with brine and dried over Na2SO4. The solution was filtered and the filtrate was evaporated onto silica gel and purified by flash chromatography (Isco, (120 gram)) eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97) to give a white amorphous solid. MS (ESI, pos. ion) m/z: 499.1 (M+1). IC50 (uM) +++++.

후처리

  1. temperaturewas heated in a 100 mL round bottom flask
  2. customequipped with a Dean-Stark trap
  3. temperaturereflux condenser under an atmosphere of nitrogen
  4. customAfter 1 h the solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in THF (8 mL) and to the solution
  6. additionwas added dropwise
  7. customresulting in a reddish solution
  8. customAfter 2 h the reaction was quenched with saturated NH4Cl
  9. customThe mixture was partitioned between EtOAc/saturated NaHCO3
  10. washThe organic layer was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationThe solution was filtered
  13. customthe filtrate was evaporated onto silica gel
  14. custompurified by flash chromatography (Isco, (120 gram))
  15. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97)
  16. customto give a white amorphous solid

출처 및 근거

ORD 기록
ord-e2dc04458d18422787a1b694b55ab863
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318718B2

반응 노트

불러오는 중…