Benzylamine → HCID 24879762, compound

HRID 1889611Notes

Reaction equation

HRID 1889611 reaction equation
N1(O[C:11]2[C:12]3[N:13]=[CH:14][N:15]([C:38]=3[N:39]=[CH:40][N:41]=2)[C@@H:16]2[O:37][C@H:27]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@@H:18]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH2:17]2)C2C=CC=CC=2N=N1.[CH2:42]([NH2:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC>[Si:20]([O:19][C@@H:18]1[C@@H:27]([CH2:28][O:29][Si:30]([C:33]([CH3:35])([CH3:36])[CH3:34])([CH3:31])[CH3:32])[O:37][C@@H:16]([N:15]2[C:38]3[N:39]=[CH:40][N:41]=[C:11]([NH:49][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[C:12]=3[N:13]=[CH:14]2)[CH2:17]1)([C:23]([CH3:25])([CH3:26])[CH3:24])([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 10796Cesium carbonateHCID 24805984HCID 24805984, compound

Product 1

HCID 24879762HCID 24879762, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

As described for the synthesis of 6-(morpholin-1-yl)-9-[2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuranosyl]purine, the benzyl derivative was prepared by a reaction between O6-(benzotriazol-1-yl)-3′,5′-bis-O-(tert-butyldimethylsilyl)-2′-deoxyinosine (26) (59.8 mg, 0.100 mmol) and benzylamine (21.8 μL, 0.200 mmol) in the presence of Cs2CO3 (65.2 mg, 0.200 mmol) in dry DME (1.0 mL) at room temperature over 6 h. Chromatographic purification (SiO2, elution with 20% EtOAc in hexanes followed by 50% EtOAc in hexanes) afforded 35.0 mg (84% yield) of the title compound as a clear gum. Rf (3% MeOH in CH2Cl2)=0.07. 1H NMR (500 MHz, CDCl3): δ 8.41 (s, 1H, Ar—H), 8.11 (s, 1H, Ar—H), 7.38 (d, 2H, Ar—H, J=7.5), 7.33 (t, 2H, Ar—H, J=7.6), 7.28 (m, 1H, Ar—H), 6.45 (t, 1H, H-1′, J=6.6), 5.98 (br s, 1H, NH), 4.87 (br s, 2H, CH2), 4.61 (m, 1, H-3′), 4.01 (q, 1H, H-4′, J=3.4), 3.87 (dd, 1H, H-5′, J=5.9, 4.4), 3.77 (dd, 1H, H-5′, J=5.9, 4.4), 2.64 (quint, 1H, H-2′. J=6.3), 2.43 (ddd, 1H, H-2′, J=13.2, 6.4, 3.9), 0.91 (s, 18H, tert-Bu), 0.10, 0.09, 0.08 (3 s, 12H, SiCH3). 13C NMR (126 MHz, CDCl3): δ 154.6, 153.1, 138.4, 128.6, 127.8, 127.5, 120.2, 87.8, 84.3, 71.2, 62.8, 41.2, 25.9, 25.8, 18.4, 18.0, −4.7, −4.8, −5.4, −5.5. FAB HRMS calcd for C29H48N5O3Si2 (M++H) 570.3296. found 570.3279.

Workup

  1. customChromatographic purification (SiO2, elution with 20% EtOAc in hexanes followed by 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0b95434d1c8b40c19f7678454e9b6ffd
Source dataset
uspto-grants-2013_08
Patent number
US08501931B2

Reaction notes

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