Methylamine ethanol → 8-[2-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-yl)-ethyl]-3-(3-methylamino-propyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one

HRID 1294574

反応式

HRID 1294574 の反応式
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:9](=[O:10])[C:8]2([CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH:18]3[CH2:23][CH2:22][CH:21]4[CH2:24][CH:19]3[C:20]4([CH3:26])[CH3:25])[CH2:12][CH2:11]2)[N:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:6]1.[CH3:33][NH2:34].CCO>O.CCOC(C)=O.[I-].[Na+]>[CH3:26][C:20]1([CH3:25])[CH:19]2[CH2:24][CH:21]1[CH2:22][CH2:23][CH:18]2[CH2:17][CH2:16][N:13]1[CH2:12][CH2:11][C:8]2([N:7]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:6][N:5]([CH2:4][CH2:3][CH2:2][NH:34][CH3:33])[C:9]2=[O:10])[CH2:15][CH2:14]1

参加物

6

反応物 2

HCID 22028356Methylamine ethanolHCID 589064433-(3-Chloro-propyl)-8-[2-(6,6-dimethyl-bicyclo[3.1.1]hept-2-yl)-ethyl]-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one

生成物 1

HCID 112363378-[2-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-yl)-ethyl]-3-(3-methylamino-propyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one収率 52.2%

試薬・触媒・溶媒 3

HCID 5238Sodium Iodide触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

The crude spiro compound (23) (162.8 g; 0.36 mol) was dissolved in methylamine/EtOH solution (Fluka, 8M; 1154 ml; 9.23 mol). Sodium iodide (2.16 g; 0.014 mol) was added and the solution was stirred at 70° C. under N2-atmosphere for 3 days. After cooling the reaction mixture was diluted with water and EtOAc (500 ml each). The aqueous layer was extracted with EtOAc (3×800 ml). The organic layer was washed with brine (500 ml). After drying on Na2SO4 the solvent was evaporated to yield a yellow oil. This oil was purified by column chromatography (SiO2; CH2Cl2/MeOH 90:10; containing 1% 7N NH3/MeOH) to yield 30 g of (24) with a purity of 93% (according to HPLC/MS) and 85 g of (24) with a purity of 96% (115 g; 0.25 mol; 70%).

後処理

  1. temperatureAfter cooling the reaction mixture
  2. extractionThe aqueous layer was extracted with EtOAc (3×800 ml)
  3. washThe organic layer was washed with brine (500 ml)
  4. customAfter drying on Na2SO4 the solvent
  5. customwas evaporated
  6. customto yield a yellow oil
  7. customThis oil was purified by column chromatography (SiO2; CH2Cl2/MeOH 90:10; containing 1% 7N NH3/MeOH)

出典と根拠

ORDレコード
ord-9cab9986065f42eb9aadb90d095cd1d8
出典データセット
uspto-grants-2007_07
特許番号
US07241770B2

関連ノート

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