2-(Dimethylamino)ethanol → (2R,3R,4S,5R)-2-{2-{[2-(Dimethylamino)ethoxy]methyl}-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol

HRID 2268379Notes

Reaction equation

HRID 2268379 reaction equation
CC(C)([O-])C.[K+].CS([O:11][CH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@H:22]2[C@H:26]([O:27][Si](C(C)(C)C)(C)C)[C@H:25]([O:35][Si](C(C)(C)C)(C)C)[C@@H:24]([CH2:43][O:44][CH3:45])[O:23]2)=[C:15]([NH:46][CH2:47][CH:48]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[N:14]=1)(=O)=O.[CH3:61][N:62]([CH2:64][CH2:65]O)[CH3:63]>CN(C)C=O>[CH3:61][N:62]([CH3:63])[CH2:64][CH2:65][O:11][CH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@H:22]2[C@H:26]([OH:27])[C@H:25]([OH:35])[C@@H:24]([CH2:43][O:44][CH3:45])[O:23]2)=[C:15]([NH:46][CH2:47][CH:48]([C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[N:14]=1

Participants

5

Reactant 3

HCID 79022-(Dimethylamino)ethanolHCID 23665647Potassium tert-butoxideHCID 86757641{9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl methanesulfonate

Product 1

HCID 9959537(2R,3R,4S,5R)-2-{2-{[2-(Dimethylamino)ethoxy]methyl}-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiolYield 23.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium tert butoxide (112 mg, 1 mmol) was added to a stirred solution of {9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl methanesulfonate (200 mg, 0.25 mmol) (preparation 16) and 2-(N,N-dimethylamino)ethanol (0.16 ml, 1.5 mmol) in N,N-dimethylformamide (3 ml). The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (30 ml) after 30 min. The aqueous phase was extracted with dichloromethane (60 ml). The organic phase was separated, dried with anhydrous magnesium sulfate and the solvent removed under reduced pressure to give a residue that was azeotroped with toluene to remove traces of N,N-dimethylformamide. This was then purified by column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol:ammonia (94:5:1) increasing in polarity to (84:14:2) to give the title compound (33 mg) as a foam. MS: 563 (MH+).

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution (30 ml) after 30 min
  2. extractionThe aqueous phase was extracted with dichloromethane (60 ml)
  3. customThe organic phase was separated
  4. dry with materialdried with anhydrous magnesium sulfate
  5. customthe solvent removed under reduced pressure
  6. customto give a residue that
  7. customwas azeotroped with toluene
  8. customto remove traces of N,N-dimethylformamide
  9. customThis was then purified by column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol:ammonia (94:5:1)
  10. temperatureincreasing in polarity to (84:14:2)

Sources & evidence

ORD record
ord-13e450efcc29462698281234e309882f
Source dataset
uspto-grants-2001_12
Patent number
US06326359B1

Reaction notes

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