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

HRID 1880152ノート

反応式

HRID 1880152 の反応式
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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
200 °C

実験手順

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) +++++.

後処理

  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

出典と根拠

ORDレコード
ord-3824d552d10e4191a71ae1dedbae968f
出典データセット
uspto-grants-2012_11
特許番号
US08318718B2

反応ノート

読み込み中…