Structure of 38324-83-3
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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. : | 38324-83-3 |
Formula : | C5H4N2O3 |
M.W : | 140.10 |
SMILES Code : | O=C(C1=CN=C(O)N=C1)O |
MDL No. : | MFCD08236864 |
InChI Key : | CRCVTNHORFBTSX-UHFFFAOYSA-N |
Pubchem ID : | 10510934 |
GHS Pictogram: |
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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 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 31.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
83.31 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.12 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.0 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.24 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.9 |
Solubility | 17.5 mg/ml ; 0.125 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.0 |
Solubility | 14.0 mg/ml ; 0.1 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.42 |
Solubility | 52.8 mg/ml ; 0.377 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 |
-7.36 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 |
0.56 |
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) |
1.34 |
* 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 trichlorophosphate; at 80.0℃; for 16h; | 2-(2-Chloro-pyrimidin-5-yl)-1-propyl-1H-benzoimidazole A suspension of <strong>[38324-83-3]2-hydroxy-pyrimidine-5-carboxylic acid</strong> (300 mg, 2.14 mmol) [J. Arukwe, K. Undheim, Acta. Chem. Scand. (1986) B40, 764-767], in POCl3 (20 ml) was heated to 80 C. for 16 h. The excess of POCl3 was evaporated and the residue was dried in HV for 2 h. The crude product was then taken up in anhydrous THF (30 ml), treated with N-propyl-benzene-1,2-diamine (354 mg, 2.36 mmol) and the solution was stirred for 1 h at RT. The mixture was then concentrated in vacuo. Purification by flash chromatography (100:0 to 75:25) afforded 2-(2-chloro-pyrimidin-5-yl)-1-propyl-1H-benzoimidazole (63 mg, 11%). UPLC (5-100% CH3CN): tR=0.974 min, MS (ES+): 273 [M+1]. | |
With trichlorophosphate; at 80.0℃; for 48h; | 7-Chloro-2-(2-chloro-pyrimidin-5-yl)-1-propyl-1H-benzoimidazole A suspension of <strong>[38324-83-3]2-hydroxy-pyrimidine-5-carboxylic acid</strong> (3.25 g, 23.2 mmol) [J. Arukwe, K. Undheim (1986) Acta. Chem. Scand., B40, 764-767], in POCl3 (100 ml) was heated to 80 C. for 48 h. The excess of POCl3 was evaporated and the residue was dried in HV for 2 h. The crude product was then taken up in anhydrous THF (30 ml), treated with 3-chloro-N-2-propyl-benzene-1,2-diamine (4.35 g, 23.6 mmol) and the solution was stirred for 20 h at RT. The mixture was then concentrated in vacuo. Purification by flash chromatography (DCM/MeOH 100:0 to 85:15) provided 7-chloro-2-(2-chloro-pyrimidin-5-yl)-1-propyl-1H-benzoimidazole (40% pure, 8.0 g, 46%). UPLC (5-100% CH3CN): tR=1.462 min, MS (ES+): 307 [M+1]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate; at 80.0℃; for 16 - 48h;Product distribution / selectivity; | 2-(2-Chloro-pyrimidin-5-yl)-1 -propyl-1 H-benzoimidazoleA suspension of <strong>[38324-83-3]2-hydroxy-pyrimidine-5-carboxylic acid</strong> (300 mg, 2.14 mmol) [J. Arukwe, K. Undheim, Acta. Chem. Scand. (1986) B40, 764-767], in POCI3 (20 ml) was heated to 80 0C for 16 h. The excess of POCI3 was evaporated and the residue was dried in HV for 2 h. 7-Chloro-2-(2-chloro-pyrimidin-5-yl)-1 -propyl-1 H-benzoimidazoleA suspension of <strong>[38324-83-3]2-hydroxy-pyrimidine-5-carboxylic acid</strong> (3.25 g, 23.2 mmol) [J. Arukwe, K.Undheim (1986) Acta. Chem. Scand., B40, 764-767], in POCI3 (100 ml) was heated to 80 0C for 48 h. The excess of POCI3 was evaporated and the residue was dried in HV for 2 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(2R,4R)-4-Amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester (HCl salt; 200 mg, 572 mumol, 1.0 eq.) and <strong>[38324-83-3]2-hydroxypyrimidine-5-carboxylic acid</strong> (88.1 mg, 629 mumol) were suspended in DMF (5.0 mL). HATU (239 mg, 629 mumol) was added followed by DIPEA (299 muL), and the resulting mixture was stirred at room temperature until the reaction was complete (2 hours). The mixture was divided into two equal portions and both solutions were concentrated. One portion was purified by preparative HPLC (10-70% MeCN/H2O) to produce compound A as a TFA salt (59.2 mg). MS m/z [M+H]+ calc'd for C24H25N3O5, 436.18. found 436.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10.8 g | With water; potassium hydroxide; In 1,4-dioxane;Inert atmosphere; Reflux; | Under nitrogen protection, 2-chloro-5-bromopyrimidine (19.3 g, 0.1 mol) and 35 mL of diethoxymethane were added to a three-neck reaction flask. Then cool down to -70 C to -60 C, A 2.2 M n-hexyllithium/hexane solution (48 mL, 0.11 mol) was initially added dropwise. After the addition is completed, the incubation reaction is continued for 1 hour. Then start adding Boc2O (22.9g, 0.105mol) The solution dissolved in diethoxyhexane (35 mL) was allowed to stand for 2 hours after the completion of the dropwise addition. Sampling detection reaction is over, the reaction was quenched by the addition of water. After layering, the organic layer was spun dry, and 2 M aqueous KOH (150 mL, 0.3 mol) and dioxane (110 mL) were added to warm to reflux for 5-6 hours.Then add 10% hydrochloric acid to adjust the pH<1 and stir the reaction for 3-4 hours, then add 1M potassium hydroxide to adjust the pH=4-5, layer, and wash the organic layer with saturated brine twice. Dry over anhydrous magnesium sulfate. Filter to dry the solvent, it is recrystallized by adding an ethanol/water mixed solvent, and dried under vacuum. 10.8 g of an off-white solid 2-hydroxypyrimidine-5-carboxylic acid was obtained, HPLC: 99.9%, yield 77%. |
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