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

HRID 1751086ノート

反応式

HRID 1751086 の反応式
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].Cl[CH2:33][CH2:34][CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]([CH:45]2[CH2:47][CH2:46]2)[C:37]1=[O:48].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH:45]1([N:38]2[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[N:36]([CH2:35][CH2:34][CH2:33][N:9]3[CH2:8][CH2:7][C:6]4([N:5]([C:12]5[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=5)[CH2:4][N:3]([CH2:18][C:19]5[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=5[C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[C:2]4=[O:1])[CH2:11][CH2:10]3)[C:37]2=[O:48])[CH2:47][CH2:46]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 66652177Tert-butyl 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

生成物 1

HCID 58046683tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate収率 76.2%

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 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (200 mg, 0.475 mmol, 1 equiv), 1-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-one (118.75 mg, 0.475 mmol, 1 equiv), sodium iodide (28.5 mg, 0.19 mmol, 0.4 equiv) and potassium carbonate (131.3 mg, 0.95 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 (230 mg, 76%); 1H NMR (400 MHz, DMSO-d6): δ 0.85-0.89 (m, 2H); 0.95-1.04 (m, 2H); 1.57 (s, 9H); 1.67 (d, 2H, J=12.4 Hz); 1.81 (t, 2H, J=6.4 and 6.8 Hz); 2.32-2.35 (t, 2H, J=6.8 Hz); 2.54-2.72 (m, 6H); 2.86-2.89 (m, 1H); 3.84-3.88 (t, 2H, J=6.8 and 6.4 Hz); 4.62 (s, 2H); 4.84 (s, 2H); 6.76-6.79 (t, 1H, J=7.2 Hz); 6.84-6.86 (d, 2H, J=8.4 Hz); 7.03-7.06 (t, 2H, J=5.6 and 6.8 Hz); 7.19-7.27 (m, 5H); 7.39-7.43 (t, 1H, J=7.6 and 7.2 Hz); 7.56-7.59 (t, 1H, J=8 and 6.4 Hz); 7.82-7.84 (d, 1H, J=7.6 Hz); MS for C38H45N5O4 m/z 636.12 (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-5820ee23636740af8504bf87dfed9983
出典データセット
uspto-grants-2015_10
特許番号
US09156840B2

反応ノート

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