Morpholine → HCID 68467595, compound

HRID 1889609Notes

Reaction equation

HRID 1889609 reaction equation
N1(O[C:11]2[C:12]3[N:13]=[CH:14][N:15]([C:24]=3[N:25]=[CH:26][N:27]=2)[C@@H:16]2[O:23][C@H:20]([CH2:21][OH:22])[C@@H:18]([OH:19])[CH2:17]2)C2C=CC=CC=2N=N1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC>[C@@H:16]1([N:15]2[CH:14]=[N:13][C:12]3[C:24]2=[N:25][CH:26]=[N:27][C:11]=3[N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[O:23][C@H:20]([CH2:21][OH:22])[C@@H:18]([OH:19])[CH2:17]1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 86643433HCID 86643433, compound

Product 1

HCID 68467595HCID 68467595, compoundYield 52%

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, this morpholino derivative was prepared by a reaction between O6-(benzotriazol-1-yl)-2′-deoxyinosine (28) (36.9 mg, 0.100 mmol), and morpholine (17.5 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 1 h. Chromatographic purification (SiO2, elution with 5% MeOH in CH2Cl2) afforded 16.6 mg (52% yield) of the title compound as a clear gum. Rf (10% MeOH in CH2Cl2)=0.34. 1H NMR (500 MHz, CDCl3): δ 8.26 (s, 1H, Ar—H), 7.77 (s, 1H, Ar—H), 6.88 (br, 1H, OH, CD3OD exchangeable), 6.30 (dd, 1H, H-1′, J=9.8, 5.4), 4.77 (d, 1H, H-3′, J=4.8), 4.30 (br, 4H, 2CH2), 4.21 (br s, 1H, H-4′), 3.96 (dd, 1H, H-5′, J=12.7, 1.2), 3.81 (t, 4H, 2CH2, J=4.9), 3.77 (br d, 1H, H-5′, J=13.2), 3.10 (ddd, 1H, H-2′, J=13.7, 9.3, 4.9), 2.65 (br, 1H, OH, CD3OD exchangeable), 2.26 (dd, 1H, H-2′, J=13.7, 5.6). 13C NMR (126 MHz, CDCl3): δ 154.1, 151.6, 149.4, 138.3, 121.7, 89.7, 87.8, 73.6, 67.0, 63.5, 45.6, 40.5.

Workup

  1. customChromatographic purification (SiO2, elution with 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-73148df82ed843828002a29ed0fb5ad9
Source dataset
uspto-grants-2013_08
Patent number
US08501931B2

Reaction notes

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