Cesium carbonate → 2',3',5'-Tris-o-(tert-butyldimethylsilyl)-8-(3-pyridinyl)adenosine

HRID 1689621Notes

Reaction equation

HRID 1689621 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:17]1[N:18]([C:49]2[N:50]=[CH:51][N:52]=[C:53]([NH2:56])[C:54]=2[N:55]=1)[C@@H:19]1[O:48][C@H:38]([CH2:39][O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[C@@H:29]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@H:20]1[O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCOC(C)=O>[Si:22]([O:21][C@@H:20]1[C@H:29]([O:30][Si:31]([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:33])[CH3:32])[C@@H:38]([CH2:39][O:40][Si:41]([C:44]([CH3:45])([CH3:46])[CH3:47])([CH3:42])[CH3:43])[O:48][C@H:19]1[N:18]1[C:49]2[N:50]=[CH:51][N:52]=[C:53]([NH2:56])[C:54]=2[N:55]=[C:17]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)([C:25]([CH3:27])([CH3:28])[CH3:26])([CH3:23])[CH3:24]

Participants

8

Reactant 3

HCID 10796Cesium carbonate2×HCID 27343783-Pyridinylboronic acidHCID 109304658-Bromo-2',3',5'-tris-o-(tert-butyl-dimethylsilyl)adenosine

Product 1

HCID 669067752',3',5'-Tris-o-(tert-butyldimethylsilyl)-8-(3-pyridinyl)adenosine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Pyridine-3-boronic acid (0.59 g, 0.48 mmol) and Cs2CO3 (3.11 g, 9.57 mmol) were added to a solution of 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-8-bromoadenosine (13) (2.20 g, 3.19 mmol) and Pd(PPh3)4 (0.37 g, 0.32 mmol) in dioxane (50 ml) under argon. Water (10 ml) was added to dissolve all Cs2CO3. The solution was heated under reflux overnight. EtOAc (200 ml) was added to the cold reaction mixture, the resultant solution shaken with water (100 ml), the organic solution dried (MgSO4), evaporated and the residual material subjected to flash chromatography on silica gel using EtOAc:MeOH 99:1; yield 1.76 g (80%). HRESI: M+H 687.3900. Calc. for C33H58N6O4Si3+H, 687.3900. 1H NMR: (300 MHz, CDCl3); δ −0.41/−0.12/0.01/0.02/0.09/0.11 (18H, s, 3×Si(CH3)2), 0.67/0.85/0.86 (27H, s, 3×SiC(CH3)3), 3.71-4.12 (3H, m, H-5′, H-3′ or H-4′), 4.53-4.55 (1H, m, H-4′ or H-3′), 5.61-5.65 (1H, m, H-2′), 5.81 (1H, d, J 6.3 Hz, H-1′), 6.02 (2H, s, NH2), 7.38-7.42 (1H, m, H-5′), 8.09-8.12 (1H, m, H-4″), 8.30 (1H, s, H-2), 8.73-8.75 (1H, m, H-6″), 9.04-9.05 (1H, m, H-2″). 13C NMR: (75 MHz, CDCl3); δ −5.5/−5.4/−5.3/−4.7/−4.6/−4.5 (3×Si(CH3)2), 17.2/18.0/18.3 (3×SiC), 25.6/25.8/25.8 (3×SiC(CH3)3), 62.5 (C-5′), 71.7/72.4 (C-2′, C-3′), 85.5/88.9 (C-4′, C-1′), 120.1/123.1/125.7/136.9/149.9/150.4/151.0/151.1/152.6/155.6 (C-5, C-5″, C-3″, C-4″, C-6, C-8, C-6″, C-2″, C-2, C-4).

Workup

  1. temperatureThe solution was heated
  2. temperatureunder reflux overnight
  3. dry with materialthe organic solution dried (MgSO4)
  4. customevaporated

Sources & evidence

ORD record
ord-74dd426c73f342c5996afedc1a5d57c1
Source dataset
uspto-grants-2012_04
Patent number
US08153609B2

Reaction notes

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