Water → N-(9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-2-{[2-(1-piperidinyl)ethoxy]methyl}-9H-purin-6-yl)-N-(2,2-diphenylethyl)amine

HRID 2268419Notes

Reaction equation

HRID 2268419 reaction equation
[H-].[Na+].CS([O:7][CH2:8][C:9]1[N:17]=[C:16]2[C:12]([N:13]=[CH:14][N:15]2[C@H:18]2[C@H:22]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@H:21]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[C@@H:20]([CH2:39][O:40][CH3:41])[O:19]2)=[C:11]([NH:42][CH2:43][CH:44]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[N:10]=1)(=O)=O.[N:57]1([CH2:63][CH2:64]O)[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1.O>O1CCCC1>[Si:24]([O:23][C@@H:22]1[C@H:21]([O:31][Si:32]([C:35]([CH3:38])([CH3:36])[CH3:37])([CH3:33])[CH3:34])[C@@H:20]([CH2:39][O:40][CH3:41])[O:19][C@H:18]1[N:15]1[CH:14]=[N:13][C:12]2[C:16]1=[N:17][C:9]([CH2:8][O:7][CH2:64][CH2:63][N:57]1[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1)=[N:10][C:11]=2[NH:42][CH2:43][CH:44]([C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([C:27]([CH3:29])([CH3:30])[CH3:28])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 18232N-PiperidinoethanolHCID 24758Sodium hydrideHCID 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 69534113N-(9-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(methoxymethyl)tetrahydro-2-furanyl]-2-{[2-(1-piperidinyl)ethoxy]methyl}-9H-purin-6-yl)-N-(2,2-diphenylethyl)amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (24 mg of an 80% dispersion in mineral oil, 0.81 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 (500 mg, 0.63 mmol) (preparation 16) and 2-(1-piperidinyl)-1-ethanol) (105 mg, 0.81 mmol) in tetrahydrofuran (5 ml). The reaction mixture was stirred for 24 hr at room temperature and then heated at reflux for a further 8 hr. The reaction mixture was then poured into cold water and extracted with ethyl acetate. The organic phase was separated, washed with brine and dried with anhydrous sodium sulfate. The solvent was then removed under reduced pressure to give a residue which was purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol (95:5) to give the title compound (101 mg) as an oil. MS: 833 (MH+).

Workup

  1. temperatureheated
  2. temperatureat reflux for a further 8 hr
  3. extractionextracted with ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried with anhydrous sodium sulfate
  7. customThe solvent was then removed under reduced pressure
  8. customto give a residue which
  9. customwas purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol (95:5)

Sources & evidence

ORD record
ord-f97996a9320b42f28ea3d22c9c3cf446
Source dataset
uspto-grants-2001_12
Patent number
US06326359B1

Reaction notes

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