Structure of 6-Amino-1-methyluracil
CAS No.: 2434-53-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 2434-53-9 |
| Formula : | C5H7N3O2 |
| M.W : | 141.13 |
| SMILES Code : | O=C1NC(C=C(N)N1C)=O |
| MDL No. : | MFCD00075366 |
| InChI Key : | GZLZRPNUDBIQBM-UHFFFAOYSA-N |
| Pubchem ID : | 75520 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 10 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.2 |
| Num. rotatable bonds | 0 |
| Num. H-bond acceptors | 2.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 36.99 |
| TPSA ? Topological Polar Surface Area: Calculated from |
80.88 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.67 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.26 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.34 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.95 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.08 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.59 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-0.37 |
| Solubility | 60.9 mg/ml ; 0.431 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
0.06 |
| Solubility | 161.0 mg/ml ; 1.14 mol/l |
| Class? Solubility class: Log S scale |
Highly soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.64 |
| Solubility | 32.0 mg/ml ; 0.227 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-8.06 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.8 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium nitrite; In water; acetic acid; | Example 4 Synthesis of (R)-1-(5-Hydroxy xyl)-7-benzyl-3,8-dimethylxanthin (CT12407) Glacial acetic acid (4.5 ml, 75 mmol) was added to a suspension of 6-amino-1-methyluracil (5.66 g, 50 mmol) in hot (100 ml). Sodium nitrite (4.14 g) was added in portions and the reaction mixture was stirred for 1 hour. The precipitate was collected by filtration, washed with water (75 ml) and then suspended in water (100 ml). The mixture was warmed to 50° C. and sodium dithionite (10 g) was added in portions keeping the temperature of the reaction between 50-55° C. The mixture was stirred at 50° C. for 1 hr and then cooled to room temperature and filtered. The solid was washed with water (2*25 ml), acetone (2*25 ml) and dried under vacuum to provide 5,6-diamino-1-methyluracil (5.6 g). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | With hydrogenchloride; sodium nitrite; In water; at 0 - 25℃; for 2h; | 6-Amino-1-methylpyrimidine-2,4-dione (10.0 g, 70.1 mmol) was dissolved in water (100 mL). Hydrochloric acid (7 mL, 84.0 mmol, 12 N) was added dropwise at 0C while stirring. Then sodium nitrite (5.80 g, 84.2 mmol) was dissolved in water (50 mL) and added dropwise to the reaction solution to give a purple precipitate. The reaction was stirred at 25C for 2 hours, filtered and washed with cold water to give a purple solid. The solid was dissolved in water (100 mL) and sodium hydrosulphite (18.7 g, 118 mmol) was added in batches while stirring, heated to 60C and stirred for 0.5 h, cooled to 25C and stirred for 16 h, filtered, washed with cold water (50 mL), ethanol (50 mL), acetone (50 mL) respectively, and dried to give 5,6-diamino-1-methylpyrimidine-2,4-dione (8.60 g, as a pale yellow solid) with a yield of 93%. 1H NMR (400 MHz, DMSO-d6) delta 10.49(br, 1H), 6.15(br, 2H), 3.25(s, 3H), 2.95(br, 2H). MS-ESI calcd. [M + H]+ 157, found 157. |
| 93% | With hydrogenchloride; sodium nitrite; In water; at 0 - 25℃; for 2h; | 6-Amino-1-methylpyrimidin-2,4-dione (10.0 g, 70.1 mmol) was dissolved in water (100 mL), and then hydrochloric acid (7 mL, 84.0 mmol, 12N) was added dropwise at 0 C. while stirring. Sodium nitrite (5.80 g, 84.2 mmol) was dissolved in water (50 mL), which was added dropwise into the reactants, then a purple precipitate appeared. The reaction solution was stirred 25 C. for 2 hours, the then was filtered. The filtrate was washed with cold water to give a purple solid. The solid was dissolved in water (100 mL), and then sodium hypodisulfite (18.7 g, 118 mmol) was added in batches while stirring. The reaction solution was heated to 60 C. and stirred for 0.5 hour, and then was cooled to 25 C. and stirred for 16 hours. The reaction solution was filtered and the filtrate was washed with water (50 mL), ethanol (50 mL) and propanone (50 mL), respectively, followed by drying to give a product 5,6-diamino-1-methylpyrimidin-2,4-dione (8.60 g, pale yellow solid), with a yield of 93%. 1H NMR (400 MHz, DMSO-d6) delta10.49 (s, 1H), 6.15 (s, 2H), 3.25 (s, 3H), 2.95 (s, 2H). MS-ESI calculated value: [M+H]+ 157; measured value: 157. |
| 78% | With ammonium hydroxide; sodium dithionite; at 50℃; for 1h; | The purple solid (3 g, 17.6 mmol) and 25% aqueous ammonia (30 ml) were added to a 100 ml reaction flask, and sodium dithionite (10.8 g, 61.6 mmol) was added in portions and stirred at 50 C for 1 h, and the reaction solution was cooled to room temperature. The reaction was stirred at room temperature for 8 h, filtered, and the filter cake was washed with ice water (10 ml) and icedLight yellow solid (2.15g, 78%) |
| With sodium nitrite; In water; acetic acid; | Example 4 Synthesis of (R)-1-(5-Hydroxyhexyl)-7-benzyl-3,8-dimethylxanthine (CT12407) Glacial acetic acid (4.5 ml, 75 mmol) was added to a suspension of 6-amino-1-methyluracil (5.66 g, 50 mmol) in hot water (100 ml). Sodium nitrite (4.14 g) was added in portions and the reaction mixture was stirred for 1 hour. The precipitate was collected by filtration, washed with water (75 ml) and then suspended in water (100 ml). The mixture was warmed to 50 C. and sodium dithionite (10 g) was added in portions keeping the temperature of the reaction between 50-55 C. The mixture was stirred at 50 C. for 1 hr and then cooled to room temperature and filtered. The solid was washed with water (2*25 ml), acetone (2*25 ml) and dried under vacuum to provide 5,6-diamino-1-methyluracil (5.6 g). | |
| With sodium nitrite; In water; acetic acid; | A. Preparation of 5,6-Diamino-1-methyluracil Glacial acetic acid (4.5 ml 75 mmol) was added to a suspension of 6-amino-1-methyluracil (5.66 g, 50 mmol) in hot water (100 ml). Sodium nitrite (4.14 g) was added in portions and the reaction mixture was stirred for 1 hour. The resulting solid was collected by filtration, washed with water (75 ml) and resuspended in water (100 ml). | |
| With sodium nitrite; In water; acetic acid; | Example 4 Synthesis of (R)-1-(5-Hydroxyhexyl)-7-benzyl-3,8-dimethylxanthine (CT12407) Glacial acetic acid (4.5 ml, 75 mmol) was added to a suspension of 6-amino-1-methyluracil (5.66 g, 50 mmol) in hot water (100 ml). Sodium nitrite (4.14 g) was added in portions and the reaction mixture was stirred for 1 hour. The precipitate was collected by filtration, washed with water (75 ml) and then suspended in water (100 ml). The mixture was warmed to 50 C. and sodium dithionite (10 g) was added in portions keeping the temperature of the reaction between 50-55 C. The mixture was stirred at 50 C. for 1 hr and then cooled to room temperature and filtered. The solid was washed with water (2*25 ml), acetone (2*25 ml) and dried under vacuum to provide 5,6-diamino-1-methyluracil (5.6 g). |


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