1,1-Dichloroethane → 2-amino-9-[(2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-purin-6-one

HRID 1017252

反応式

HRID 1017252 の反応式
C([NH:4][C:5]1[NH:6][C:7](=[O:14])[C:8]2[NH:9][CH:10]=[N:11][C:12]=2[N:13]=1)(=O)C.ClC(Cl)C.C(C([C@:24]([C:48](=[O:55])C1C=CC=CC=1)([C@:26](C(=O)C1C=CC=CC=1)([C@H:28]([CH2:30][O:31]C(=O)C1C=CC=CC=1)[OH:29])[OH:27])O)=O)(=O)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>N1C=CC=CC=1.C(Cl)Cl>[CH:10]1[N:11]([C@H:30]2[O:31][C@@H:24]([CH2:48][OH:55])[C@H:26]([OH:27])[C@@H:28]2[OH:29])[C:12]2[NH:13][C:5]([NH2:4])=[N:6][C:7](=[O:14])[C:8]=2[N:9]=1

参加物

7

反応物 4

HCID 63651,1-Dichloroethane2 回HCID 65367Trimethylsilyl triflateHCID 699334681-acetyl-2,3,5-O-tribezoyl-L-riboseHCID 135432176N-(6,7-dihydro-6-oxo-1H-purin-2-yl)acetamide

生成物 1

HCID 1785089292-amino-9-[(2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-purin-6-one

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

N2-Acetylguanine (4.125 g, 21.35 mmol) was suspended in pyridine (50 mL) at 80° C. for 25 min. and then pyridine was evaporated under high vacuum. The same, procedure was repeated once. The obtained material was dried under vacuum overnight and silylated by heating with excess of HMDS (50 mL), pyridine (10 mL) and TMSCl (150 mL) under argon for 2.5 hours. After the reaction mixture was cooled to RT, the solvents were evaporated under vacuum. The residual HMDS and pyridine were coevaporated with xylene (2×40 mL). The silylated base was suspended in dichloroethane (70 mL) and combined with dichloroethane (182 mL) solution of 1-acetyl-2,3,5-O-tribezoyl-L-ribose (9.71 g, 19.22 mmol). The obtained suspension was stirred under argon at reflux temperature for 10 min. and dichloroethane (35 mL) solution of TMS-triflate (4.50 mL, 23.276 mmol) was added dropwise (20 min). The obtained reaction mixture was stirred under reflux for 1.5 h, cooled to RT and diluted with methylene chloride (500 ml). The organic solution was washed with cold NaHCO3 (5% aq., 2×150 mL), brine (150 mL), dried. (Na2SO4) and evaporated to dryness. The reaction mixture was purified by flash chromatography (400 g of silica gel, eluent: 28% EtOAc, 2% EtOH in CH2Cl2, v/v) to give 5.60 g (46%) of N2-Acetyl-2′,3′,5′-O-tribenzoyl-∃-L-guanosine 5.

後処理

  1. custompyridine was evaporated under high vacuum
  2. customThe obtained material was dried under vacuum overnight
  3. temperaturesilylated by heating with excess of HMDS (50 mL), pyridine (10 mL) and TMSCl (150 mL) under argon for 2.5 hours
  4. customthe solvents were evaporated under vacuum
  5. temperatureat reflux temperature for 10 min.
  6. customThe obtained reaction mixture
  7. stirringwas stirred
  8. temperatureunder reflux for 1.5 h
  9. temperaturecooled to RT
  10. washThe organic solution was washed with cold NaHCO3 (5% aq., 2×150 mL), brine (150 mL)
  11. customdried
  12. custom(Na2SO4) and evaporated to dryness
  13. customThe reaction mixture was purified by flash chromatography (400 g of silica gel, eluent: 28% EtOAc, 2% EtOH in CH2Cl2, v/v)

出典と根拠

ORDレコード
ord-33bfc9f012404fe1b950c1f96b374157
出典データセット
uspto-grants-2002_11
特許番号
US06479463B1

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