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

HRID 2038185노트

반응식

HRID 2038185 반응식
[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

참가 물질

6

반응물 3

HCID 108982-BromoethanolHCID 81531Diisopropylethylamine2회HCID 583062032-(Butyloxy)-8-(methyloxy)-9-(4-piperidinylmethyl)-9H-purin-6-amine2회

생성물 1

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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b5aec0438f634c34afb9c0f135d17de4
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575340B2

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