Triethylamine → 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]-purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diol

HRID 547256

Reaction equation

HRID 547256 reaction equation
C([N:3]([CH2:6][CH3:7])CC)C.[Cl:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3Cl)[C@H:12]([OH:25])[C@@H:11]1[OH:26]>C(O)(C)C>[OH:14][C@@H:13]1[CH2:12][CH2:11][CH2:7][C@H:6]1[NH:3][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[C:21]=1[N:22]=[CH:23][N:15]2[CH:13]1[C@H:12]([OH:25])[C@H:11]([OH:26])[C@@H:10]([CH2:9][Cl:8])[O:14]1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 11529600(4S,5S,2R,3R)-5-(chloromethyl)-2-(6-chloropurin-9-yl)oxolane-3,4-diol

Product 1

HCID 671894862-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]-purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diolYield 309.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

To a suspension of (R,R)-2-aminopentanol hydrochloride (34.2 g, 249 mmol) in degassed isopropanol (100 ml) and distilled triethylamine (dried over calcium hydride, 95 ml, 69 g, 226 mmol) was added dropwise a solution of (4S,5S,2R,3R)-5-(chloromethyl)-2-(6-chloropurin-9-yl)oxolane-3,4-diol (36.3 g, 118.7 mmol) in 400 ml of isopropanol. The reaction mixture was stirred at room temperature for 30 minutes, and then refluxed (oil bath temperature: ˜80° C.) for 20 hours. After cooling the reaction mixture to ambient temperature, the solvent was removed under reduced pressure, and 1000 ml of water was added to the residue. The suspension was stirred at room temperature for 3.5 hours, and the solid material filtered off, washed with water (1×60 ml and 1×90 ml), and dried under vacuum over P2O5 for 3 days to yield 68.0 g (81%) of 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diol as a light brown powder.

Workup

  1. temperaturerefluxed (oil bath temperature: ˜80° C.) for 20 hours
  2. temperatureAfter cooling the reaction mixture to ambient temperature
  3. customthe solvent was removed under reduced pressure, and 1000 ml of water
  4. additionwas added to the residue
  5. stirringThe suspension was stirred at room temperature for 3.5 hours
  6. filtrationthe solid material filtered off
  7. washwashed with water (1×60 ml and 1×90 ml)
  8. dry with materialdried under vacuum over P2O5 for 3 days

Sources & evidence

ORD record
ord-796b60bf492b4e40b9ae713d47a8ff38
Source dataset
uspto-grants-2011_05
Patent number
US07939509B2

Linked notes

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