2-Bromoethanol → 6-Amino-2-(butyloxy)-9-{[1-(2-hydroxyethyl)-4-piperidinyl]methyl}-7,9-dihydro-8H-purin-8-one

HRID 2038185ノート

反応式

HRID 2038185 の反応式
[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:22]C)[N:12]2[CH2:15][CH:16]2CCNCC2)=[C:8]([NH2:24])[N:7]=1)[CH2:2][CH2:3][CH3:4].BrCC[OH:28].[CH3:29][CH2:30][N:31]([CH:35]([CH3:37])C)[CH:32]([CH3:34])C>CN(C=O)C.CS(C)=O>[NH2:24][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:22])[N:12]2[CH2:15][CH:16]1[CH2:34][CH2:32][N:31]([CH2:30][CH2:29][OH:28])[CH2:35][CH2:37]1

参加物

6

反応物 3

HCID 108982-BromoethanolHCID 81531Diisopropylethylamine2 回HCID 583062032-(Butyloxy)-8-(methyloxy)-9-(4-piperidinylmethyl)-9H-purin-6-amine2 回

生成物 1

HCID 673659656-Amino-2-(butyloxy)-9-{[1-(2-hydroxyethyl)-4-piperidinyl]methyl}-7,9-dihydro-8H-purin-8-one

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

2-(Butyloxy)-8-(methyloxy)-9-(4-piperidinylmethyl)-9H-purin-6-amine (for example, as prepared for Intermediate 28) (0.0335 g, 0.10 mmol) in DMF (0.4 mL) was added to 2-bromoethanol (commercially available, for example, from Aldrich) (0.0085 mL, 0.12 mmol). DIPEA (0.040 mL, 0.23 mmol) was added and the reaction mixture heated at 50° C. for 18 hours. Additional DIPEA (0.040 mL, 0.23 mmol) was added and heating continued for a further 18 hours. The reaction mixture was diluted with DMSO:MeOH (0.25 mL) and the resultant solution purified by MDAP (Method A). Appropriate fractions were combined and evaporated in vacuo. The residue was dissolved in 4M HCl in dioxane (0.2 mL) and allowed to stand at room temperature for 4 hours. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus. The residue was redissolved in methanol (0.5 mL) and applied to top of 0.1 g aminopropyl SPE (preconditioned with methanol, 1.5 mL). The cartridge was washed with methanol (1.5 mL). The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the title compound (0.0053 g).

後処理

  1. temperatureheating
  2. customMeOH (0.25 mL) and the resultant solution purified by MDAP (Method A)
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in 4M HCl in dioxane (0.2 mL)
  5. waitto stand at room temperature for 4 hours
  6. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus
  7. dissolutionThe residue was redissolved in methanol (0.5 mL)
  8. washThe cartridge was washed with methanol (1.5 mL)
  9. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus

出典と根拠

ORDレコード
ord-b5aec0438f634c34afb9c0f135d17de4
出典データセット
uspto-grants-2013_11
特許番号
US08575340B2

反応ノート

読み込み中…