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Potassium Carbonate → 6-Amino-2-(butyloxy)-9-{4-[1-(1-ethylpropyl)-4-piperidinyl]butyl}-7,9-dihydro-8H-purin-8-one

HRID 1045017
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HRID 1045017 반응식
Br[CH:2]([CH2:5][CH3:6])[CH2:3][CH3:4].[CH2:7]([O:11][C:12]1[N:20]=[C:19]2[C:15]([N:16]=[C:17]([O:31]C)[N:18]2[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[C:14]([NH2:33])[N:13]=1)[CH2:8][CH2:9][CH3:10].CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CS(C)=O>[NH2:33][C:14]1[N:13]=[C:12]([O:11][CH2:7][CH2:8][CH2:9][CH3:10])[N:20]=[C:19]2[C:15]=1[NH:16][C:17](=[O:31])[N:18]2[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]1[CH2:30][CH2:29][N:28]([CH:2]([CH2:5][CH3:6])[CH2:3][CH3:4])[CH2:27][CH2:26]1
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참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 157383-Bromopentane2회HCID 81531Diisopropylethylamine2회HCID 583062222-(Butyloxy)-8-(methyloxy)-9-[4-(4-piperidinyl)butyl]-9H-purin-6-amine

생성물 1

HCID 672336886-Amino-2-(butyloxy)-9-{4-[1-(1-ethylpropyl)-4-piperidinyl]butyl}-7,9-dihydro-8H-purin-8-one수율 13.6%

시약·촉매·용매

2
HCID 679Dimethyl Sulfoxide용매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

3-Bromopentane (0.1 mmol) was weighed into a tube and an aliquot (0.4 ml, 0.12 mmol) of a solution of 2-(butyloxy)-8-(methyloxy)-9-[4-(4-piperidinyl)butyl]-9H-purin-6-amine (0.452 g mg, 1.2 mmol) suspended in DMF (4.8 ml) was added. DIPEA (40 μl, 0.229 mmol) was added and heated at 50° C. for 18 hours. An additional portion of 3-bromopentane (15 μl) and DIPEA (40 μl) was added and heating continued for a further 18 hours. Potassium carbonate (46 mg) was added and heating continued for a further 72 hours. DMSO (200 uL) was added and the resultant mixture filtered, the solution was purified by Mass Directed AutoPrep (Method A). The solvent was evaporated in vacuo using the Genevac. The residue was redissolved in 4M HCl/dioxane (0.2 ml), capped and stood at room temperature for 18 hours. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus. The sample was dissolved in 1:1 DMSO:MeOH and purified by MDAP (Method C) and the solvent was evaporated in vacuo using the Genevac. The material was redissolved in methanol (0.5 ml), and applied to a 0.1 g aminopropyl SPE (preconditioned with methanol, 1.5 ml). The cartridge was eluted with methanol (1.5 ml), the solvent was removed to give the title compound (5.9 mg).

후처리

  1. additionwas added
  2. temperatureheating
  3. temperatureheating
  4. waitcontinued for a further 72 hours
  5. filtrationthe resultant mixture filtered
  6. customthe solution was purified by Mass Directed AutoPrep (Method A)
  7. customThe solvent was evaporated in vacuo
  8. dissolutionThe residue was redissolved in 4M HCl/dioxane (0.2 ml)
  9. customcapped
  10. waitstood at room temperature for 18 hours
  11. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus
  12. dissolutionThe sample was dissolved in 1:1 DMSO
  13. customMeOH and purified by MDAP (Method C)
  14. customthe solvent was evaporated in vacuo
  15. dissolutionThe material was redissolved in methanol (0.5 ml)
  16. washThe cartridge was eluted with methanol (1.5 ml)
  17. customthe solvent was removed

출처 및 근거

ORD 기록
ord-d4d42584fddf48059a1d88b22ce4f254
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08563717B2

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