Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
Entry | Reaction | Starting compd | Reagents and conditions | Product | Yield (%) |
---|---|---|---|---|---|
1 | demethoxylation | 2 | TMSCl, NaI, CH3CN, r.t., 20 h | 3 | 18.3 |
AcCl, reflux, 20 h, H2O, r.t., overnight | 67.8 | ||||
2 | methoxymethylation | 3 | TMSCl, CH3CN, reflux, 2 h, ( iPr)2EtN, MOMCl, 50 °C, 6 h | 4 | 22.4 |
5 | 13.4 | ||||
6 | 11 | ||||
HMDS, (NH4)2SO4, reflux, 1 h, MOMCl, r.t., overnight | 4 | 2.9 | |||
5 | 21.4 | ||||
K2CO3, DMF, MOMCl, r.t., overnight | 4 | 28.5 | |||
5 | 12.1 | ||||
6 | 15.4 | ||||
3 | debenzylation | 4 | BCl3, CH2Cl2, −70 °C, 1h | 7 | 33.4 |
8 and 9 | 24.8 | ||||
4 | 5 | BCl3, CH2Cl2, −70 °C, 4 h | 8 | 18.6 | |
15 | 60 | ||||
BCl3, CH2Cl2, −70 °C, 2 h | 8 | 31.7 | |||
5 | tritylation | 7 | MTrCl, DMAP, DMF, r.t., overnight | 10 | 46.4 |
11 | 37.5 | ||||
12 | 5.5 | ||||
6 | 8 | 12 | 30.8 | ||
7 | 15 | 16 | 26.12 | ||
17 | 9.4 |
2.2. NMR Studies
3. Experimental
3.1. General
3.2. Procedures for the Preparation of Compounds
3.2.1. 6-[(3-Benzyloxy-2-benzyloxymethyl)propyl]-5-methylpyrimidin-2,4-dione (3)
3.2.2. 6-[(3-Benzyloxy-2-benzyloxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (4), 6-[(3-benzyloxy-2-benzyloxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-dione (5) and 6-[(3-benzyloxy-2-benzyloxymethyl)propyl]-3-methoxymethyl-5-methylpyrimidin-2,4-dione (6)
3.2.3. 6-[(3-Hydroxy-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (7), 6-[(3-hydroxy-2-hydroxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-dione (8) and 6-[(3-hydroxy-2-hydroxymethyl)propyl]-3-methoxymethyl-5-methylpyrimidin-2,4-dione (9)
3.2.4. 6-[2,3-Bis(4-methoxytriphenylmethoxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (10), 6-[3-hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (11) and 6-[3-hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-dione (12)
3.2.5. 6-[(3-Fluoro-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (13), 6-[(3-hydroxy-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (7) and 4-hydroxymethyl-8-methoxymethyl-6-methyl-4,5-dihydro-pyrimido[1,6-c][1,3]oxazepine-7,9-dione (14)
3.2.6. 6-[(3-Hydroxy-2-hydroxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-dione (8) and 6-[(3-hydroxy-2-hydroxymethyl)propyl]-5-methylpyrimidin-2,4-dione (15)
3.2.7. 6-[3-Hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1-methoxymethyl-5-methyl-pyrimidin-2,4-dione (12)
3.2.8. 6-[2,3-Bis(4-methoxytriphenylmethoxymethyl)propyl]-5-methylpyrimidin-2,4-dione (16) and 6-[3-hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-5-methylpyrimidin-2,4-dione (17)
4. Conclusions
Acknowledgements
References and Notes
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Kraljević, T.G.; Petrović, M.; Krištafor, S.; Makuc, D.; Plavec, J.; Ross, T.L.; Ametamey, S.M.; Raić-Malić, S. Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains. Molecules 2011, 16, 5113-5129. https://doi.org/10.3390/molecules16065113
Kraljević TG, Petrović M, Krištafor S, Makuc D, Plavec J, Ross TL, Ametamey SM, Raić-Malić S. Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains. Molecules. 2011; 16(6):5113-5129. https://doi.org/10.3390/molecules16065113
Chicago/Turabian StyleKraljević, Tatjana Gazivoda, Martina Petrović, Svjetlana Krištafor, Damjan Makuc, Janez Plavec, Tobias L. Ross, Simon M. Ametamey, and Silvana Raić-Malić. 2011. "Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains" Molecules 16, no. 6: 5113-5129. https://doi.org/10.3390/molecules16065113