Diisopropylethylamine → 8-(3'-Benzyloxybiphenyl-4-ylmethyl-amino)-2',3',5'-tris-o-(tert-butyldimethylsilyl)adenosine

HRID 1713296Notes

Reaction equation

HRID 1713296 reaction equation
Br[C:2]1[N:3]([C:34]2[N:35]=[CH:36][N:37]=[C:38]([NH2:41])[C:39]=2[N:40]=1)[C@@H:4]1[O:33][C@H:23]([CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[C@@H:14]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[C@H:5]1[O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[CH2:42]([O:49][C:50]1[CH:51]=[C:52]([C:56]2[CH:61]=[CH:60][C:59]([CH2:62][NH2:63])=[CH:58][CH:57]=2)[CH:53]=[CH:54][CH:55]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(N(CC)C(C)C)(C)C>C(O)CC>[CH2:42]([O:49][C:50]1[CH:51]=[C:52]([C:56]2[CH:57]=[CH:58][C:59]([CH2:62][NH:63][C:2]3[N:3]([C:34]4[N:35]=[CH:36][N:37]=[C:38]([NH2:41])[C:39]=4[N:40]=3)[C@@H:4]3[O:33][C@H:23]([CH2:24][O:25][Si:26]([C:29]([CH3:30])([CH3:31])[CH3:32])([CH3:28])[CH3:27])[C@@H:14]([O:15][Si:16]([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17])[C@H:5]3[O:6][Si:7]([C:10]([CH3:13])([CH3:11])[CH3:12])([CH3:9])[CH3:8])=[CH:60][CH:61]=2)[CH:53]=[CH:54][CH:55]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 109304658-Bromo-2',3',5'-tris-o-(tert-butyl-dimethylsilyl)adenosineHCID 230050193'-Benzyloxybiphenyl-4-ylmethylamine

Product 1

HCID 674544418-(3'-Benzyloxybiphenyl-4-ylmethyl-amino)-2',3',5'-tris-o-(tert-butyldimethylsilyl)adenosineYield 83.3%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Procedure

A mixture of 8-bromo-2′,3′,5′-tris-O-(tert-butyl-dimethylsilyl)adenosine (0.660 g), 3′-benzyloxybiphenyl-4-ylmethylamine (0.832 g) and N,N-diisopropylethylamine (0.667 mL) in 1-propanol (9.6 mL) was heated under reflux with stirring for 62 hours. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate (35 mL) and 10% aqueous citric acid (10 mL). The organic layer was washed successively with 10% aqueous citric acid (10 mL×2), saturated aqueous sodium hydrogen carbonate (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on aminopropylated silica gel (eluent: hexane/ethyl acetate=2/1) to give the title compound (0.716 g).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux
  3. custompartitioned between ethyl acetate (35 mL) and 10% aqueous citric acid (10 mL)
  4. washThe organic layer was washed successively with 10% aqueous citric acid (10 mL×2), saturated aqueous sodium hydrogen carbonate (10 mL) and brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on aminopropylated silica gel (eluent: hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-a0b63de5fdc2456f988d2280abfbcb6d
Source dataset
uspto-grants-2010_09
Patent number
US07795236B2

Reaction notes

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