Sodium Iodide → tert-butyl 3-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 2363019ノート

反応式

HRID 2363019 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:34][CH2:35][CH2:36][N:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:48][CH2:47]2)[C:38]1=[O:49].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH:46]1([N:39]2[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[N:37]([CH2:36][CH2:35][CH2:34][N:15]3[CH2:14][CH2:13][C:12]4([N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH2:9][N:10]([CH2:19][C:20]5[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=5)[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[C:11]4=[O:18])[CH2:17][CH2:16]3)[C:38]2=[O:49])[CH2:48][CH2:47]1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467891-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-oneHCID 66652535Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

生成物 1

HCID 58046607tert-butyl 3-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate収率 68.3%

試薬・触媒・溶媒 1

HCID 6569Methyl Ethyl Ketone溶媒

反応条件

温度
81 °C

実験手順

A mixture of tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (163.5 mg, 0.372 mmol, 1 equiv), 1-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-one (93 mg, 0.372 mmol, 1 equiv), sodium iodide (22.3 mg, 0.15 mmol, 0.4 equiv) and potassium carbonate (102.8 mg, 0.74 mmol, 2 equiv) in 2-butanone was stirred at 81° C. for 16 h. After cooling the reaction mixture, the crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, filtered, concentrated, and the crude residue was purified using the Biotage flash chromatography system (SNAP 10 g cartridge, Rf=0.5, gradient—1%-10% methanol in dichloromethane) to afford the title compound (166 mg, 68%); MS for C38H44FN5O4 m/z 654.24 (M+H)+.

後処理

  1. temperatureAfter cooling the reaction mixture
  2. customthe crude mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe crude residue was purified

出典と根拠

ORDレコード
ord-ada7d1161c584864aa3cd35a87d2e656
出典データセット
uspto-grants-2014_04
特許番号
US08691836B2

反応ノート

読み込み中…