Potassium Carbonate → 2-{2-[(1-benzhydryl-3-azetidinyl)amino]ethyl}-9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-N-(2,2-diphenylethyl)-9H-purin-6-amine

HRID 2268424Notes

Reaction equation

HRID 2268424 reaction equation
CS(O[CH:6]1[CH2:9][N:8]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[NH2:29][CH2:30][CH2:31][C:32]1[N:40]=[C:39]2[C:35]([N:36]=[CH:37][N:38]2[C@H:41]2[C@H:45]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[C@H:44]([O:54][Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56])[C@@H:43]([CH2:62][O:63][CH3:64])[O:42]2)=[C:34]([NH:65][CH2:66][CH:67]([C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[N:33]=1>C(#N)C>[CH:10]([N:8]1[CH2:9][CH:6]([NH:29][CH2:30][CH2:31][C:32]2[N:40]=[C:39]3[C:35]([N:36]=[CH:37][N:38]3[C@H:41]3[C@H:45]([O:46][Si:47]([C:50]([CH3:51])([CH3:52])[CH3:53])([CH3:49])[CH3:48])[C@H:44]([O:54][Si:55]([C:58]([CH3:59])([CH3:60])[CH3:61])([CH3:57])[CH3:56])[C@@H:43]([CH2:62][O:63][CH3:64])[O:42]3)=[C:34]([NH:65][CH2:66][CH:67]([C:68]3[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=3)[C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)[N:33]=2)[CH2:7]1)([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonateHCID 69534061N-{2-(2-Aminoethyl)-9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-9H-purin-6-yl}-N-(2,2-diphenylethyl)amine

Product 1

HCID 867576422-{2-[(1-benzhydryl-3-azetidinyl)amino]ethyl}-9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-N-(2,2-diphenylethyl)-9H-purin-6-amineYield 51.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-Benzhydryl-3-azetidinyl methanesulfonate (90 mg, 0.28 mmol) and potassium carbonate (50 mg, 0.36 mmol) were added to a stirred solution of N-{2-(2-aminoethyl)-9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-9H-purin-6-yl}-N-(2,2-diphenylethyl)amine (200 mg) (preparation 18) in acetonitrile (3 ml). The reaction mixture was heated at reflux for 5 hr and then allowed to stand at room temperature for a further 24 hr. The resulting mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was separated and the aqueous layer extracted with more ethyl acetate. The combined organic solutions were washed with brine and dried with anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol:ammonia (98:2:0.2) to give the title compound (135 mg) as a foam. MS: 955 (MH+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 hr
  3. customThe resulting mixture was partitioned between ethyl acetate and water
  4. customThe ethyl acetate layer was separated
  5. extractionthe aqueous layer extracted with more ethyl acetate
  6. washThe combined organic solutions were washed with brine
  7. dry with materialdried with anhydrous magnesium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customthe residue purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol:ammonia (98:2:0.2)

Sources & evidence

ORD record
ord-1b460e94dac947dd8fdcefe66a1f1edf
Source dataset
uspto-grants-2001_12
Patent number
US06326359B1

Reaction notes

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