Benzimidazole → HCID 59326866、化合物

HRID 1880142ノート

反応式

HRID 1880142 の反応式
[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]

参加物

7

反応物 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

生成物 1

HCID 59326866HCID 59326866、化合物

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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) +++++.

後処理

  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

出典と根拠

ORDレコード
ord-e2dc04458d18422787a1b694b55ab863
出典データセット
uspto-grants-2012_11
特許番号
US08318718B2

反応ノート

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