Cesium carbonate → 1-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)pyrrolidin-1-yl)ethanone

HRID 410287노트

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HRID 410287 반응식
F[C:2]1[C:7]([CH:8]2[CH2:12][CH2:11][N:10]([C:13](=[O:15])[CH3:14])[CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[C:25]([C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1)=[O:26].C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.CN1C(=O)CCC1>[NH:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[C:25]([C:27]1[CH:32]=[CH:31][C:30]([O:33][C:2]2[C:7]([CH:8]3[CH2:12][CH2:11][N:10]([C:13](=[O:15])[CH3:14])[CH2:9]3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:29][CH:28]=1)=[O:26]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanoneHCID 593272171-(3-(2-Fluoropyridin-3-yl)pyrrolidin-1-yl)ethanone

생성물 1

HCID 593270971-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)pyrrolidin-1-yl)ethanone

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 13387N-methyl-2-pyrrolidone용매

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온도
200 °C

실험 절차

A glass microwave reaction vessel was charged with 1-(3-(2-fluoropyridin-3-yl)pyrrolidin-1-yl)ethanone (86 mg, 0.41 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (197 mg, 0.826 mmol), cesium carbonate (309 mg, 0.95 mmol), copper(i) iodide (79 mg, 0.413 mmol), and NMP (1.4 mL). The reaction mixture was degassed and flushed with N2 and heated in a Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 200° C. for 1 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and 1 N NH4Cl. The aqeuous layer was back extracted with EtOAc (2×) and the combined organic layer was washed with water, brine, dried (Na2SO4) and concentrated. The crude material was chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% EtOAc in hexane, then 5% MeOH in EtOAc, followed by trituration with ether, dried to provide 1-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)pyrrolidin-1-yl)ethanone as off-white solid. MS (ESI, pos. ion) m/z: 427.1 (M+1). IC50 (uM) +++++.

후처리

  1. customA glass microwave reaction vessel
  2. customThe reaction mixture was degassed
  3. customflushed with N2
  4. temperatureAfter cooling to RT
  5. customthe reaction mixture was partitioned between EtOAc and 1 N NH4Cl
  6. extractionThe aqeuous layer was back extracted with EtOAc (2×)
  7. washthe combined organic layer was washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude material was chromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  11. washeluting with a gradient of 0% to 100% EtOAc in hexane
  12. customdried

출처 및 근거

ORD 기록
ord-f0e5a7582b744fc6a19c8ee060f13ffd
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759532B2

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