Structure of 1289387-30-9
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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. : | 1289387-30-9 |
| Formula : | C6H7ClN2O |
| M.W : | 158.59 |
| SMILES Code : | COCC1=NC(Cl)=NC=C1 |
| English Name : | 2-Chloro-4-(methoxymethyl)pyrimidine |
| MDL No. : | MFCD18837162 |
| InChI Key : | LKOWHMGUHBHEDI-UHFFFAOYSA-N |
| Pubchem ID : | 53385539 |
| Num. heavy atoms | 10 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.33 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 37.9 |
| TPSA ? Topological Polar Surface Area: Calculated from |
35.01 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.9 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.85 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.12 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.01 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.82 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.14 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-1.67 |
| Solubility | 3.38 mg/ml ; 0.0213 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.17 |
| Solubility | 10.8 mg/ml ; 0.0678 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.79 |
| Solubility | 0.258 mg/ml ; 0.00163 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 |
Yes |
| 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) |
Yes |
| 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 |
-6.66 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) |
1.94 |
* 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 |
|---|---|---|
| 43 % | Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; | 3 5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazole- 4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (3) 1n (350mg, 0.94mmol) was dissolved in N,N-dimethylacetamide (20mL), 60% sodium hydride (180mg, 7.52mmol) was added under ice-cooling, reacted for 30 minutes, and 2-chloro-4-( Methoxymethyl)pyrimidine (179 mg, 1.13 mmol).React at room temperature for 30 minutes.Dilute with water (10 mL), adjust the pH to 4-5 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse phase C18 column chromatography (acetonitrile/water) and then lyophilized to obtain the title compound 3 (200 mg, yield 43 %). |
| 43 % | Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; | 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL),60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath,reacted for 30 minutes,2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added,reacted at room temperature for 30 minutes.Diluted with water (10 mL),adjusted pH to 4-5 with 1M hydrochloric acid,extracted with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by reverse phase flash column chromatography (acetonitrile/water) and then freeze-dried to obtain compound 1 (200 mg, yield 43%). |
| 43 % | Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; | 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL),60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath,reacted for 30 minutes,2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added,reacted at room temperature for 30 minutes.Diluted with water (10 mL),adjusted pH to 4-5 with 1M hydrochloric acid,extracted with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by reverse phase flash column chromatography (acetonitrile/water) and then freeze-dried to obtain compound 1 (200 mg, yield 43%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 47 % | Stage #1: 1-fluoro-5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridine-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; | 5.6 1-Fluoro-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2 ,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (5) Dissolve 5e (130mg, 0.33mmol) in N,N-dimethylacetamide (10mL), add 60% sodium hydride (107mg, 2.66mmol) under ice-cooling, react for 30 minutes, add 2-chloro-4-( Methoxymethyl)pyrimidine (106mg, 0.67mmol), react at room temperature for 30 minutes.Dilute with water (10 mL), adjust the pH to 4-5 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×2).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse-phase flash column chromatography (acetonitrile/water) to obtain compound 5 (80 mg, yield 47%) . |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 22 % | Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)-1-methyloctahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide at 20℃; | 14.6 5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-tri Azol-4-yl)-2-methylpyridin-3-yl)oxy)-1-methyloctahydropentalene-1-carboxylic acid (14) Dissolve 14e (130mg, 0.33mmol) in N,N-dimethylacetamide (10mL), add 60% sodium hydride (108mg, 2.69mmol) under ice-cooling, react for 30 minutes, add 2-chloro-4- (Methoxymethyl)pyrimidine (107mg, 0.67mmol), stirred at room temperature for 30 minutes.Add water (10 mL), adjust the pH to 5-6 with 1M hydrochloric acid, and extract with ethyl acetate (20 mL×3).The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse-phase flash column chromatography (acetonitrile/water) and then lyophilized to obtain the title product 14 (38 mg, yield rate 22%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: (1-(3-(difluoromethoxy)-4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methanol With sodium hydride In tetrahydrofuran; mineral oil Inert atmosphere; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In tetrahydrofuran; mineral oil at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: methanol / 3 h / Reflux 2: phosphorus pentachloride / 5,5-dimethyl-1,3-cyclohexadiene / 9 h / 70 - 90 °C 3: hydrogenchloride; chloro-trimethyl-silane; zinc / methanol / 16 h / 70 - 75 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: phosphorus pentachloride / 5,5-dimethyl-1,3-cyclohexadiene / 9 h / 70 - 90 °C 2: hydrogenchloride; chloro-trimethyl-silane; zinc / methanol / 16 h / 70 - 75 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78 % | With hydrogenchloride; chloro-trimethyl-silane; zinc In methanol at 70 - 75℃; | 1.3; 2.3 third step: Add intermediate 3 (1eq), zinc powder (4eq), trimethylchlorosilane (1eq) and hydrochloric acid (2eq) into methanol (10V), stir and react at 70-75°C for 16 hours, filter after cooling down, methanol /water beating to obtain 2-chloro-4-(methoxymethyl)pyrimidine (yield 78%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: 5-((6-(5-(hydroxymethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid With sodium hydride In N,N-dimethyl acetamide; mineral oil Cooling with ice; Stage #2: 2-chloro-4-(methoxymethyl)pyrimidine In N,N-dimethyl acetamide; mineral oil at 20℃; Stage #3: With ammonium hydroxide In ethanol | 1.13 Step 13: (1S, 3aS, 5S, 6aR)-5-((6-(5-(((4-(methoxymethyl)pyrimidin-2-yl)oxy)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)octahydropentalene-1-carboxylic acid (1o-P1) 1n (350 mg, 0.94 mmol) was dissolved in N,N-dimethylacetamide (20 mL), 60% sodium hydride (180 mg, 7.52 mmol) was added under ice bath, reacted for 30 minutes, 2-chloro-4-(methoxymethyl)pyrimidine (179 mg, 1.13 mmol) was added, and reacted at room temperature for 30 minutes. After the reaction was completed, water (10 mL) was added for dilution, 1 M hydrochloric acid was used to adjust the pH value to 4-5, and ethyl acetate was used for extraction (20 mL × 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by reverse phase flash column chromatography (acetonitrile/water) and freeze-dried to obtain compound 1o (200 mg, yield 43%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 68.6% | With ammonia In methanol at 100℃; for 1h; Sealed tube; | 1.136 Example 1.136. Synthesis of 4-(methoxymethyl)pyrimidin-2-amine A solution of 2-chloro-4-(methoxymethyl)pyrimidine (200 mg, 1.26 mmol) in a solution of NH3in MeOH (2 mL) was heated at 100 °C for 1 h in a sealed tube. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL× 2), dried over Na2SO4, filtered and concentrated to give 4-(methoxymethyl)pyrimidin-2-amine (120 mg, 68.6 %) as a white solid. LCMS m/z = 140.09 [M+H]+;1HNMR (400 MHz, DMSO-d6) δ 8.20 (d, J = 5.0 Hz, 1H), 6.56 (d, J = 4.2 Hz, 3H), 4.24 (s, 2H), 3.34 (s, 3H). |

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