Structure of 94741-69-2
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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.
Synonyms: 4-amino-2-chloropyrimidine-5-carbonitrile
4.5
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CAS No. : | 94741-69-2 |
Formula : | C5H3ClN4 |
M.W : | 154.56 |
SMILES Code : | N#CC1=CN=C(Cl)N=C1N |
Synonyms : |
4-amino-2-chloropyrimidine-5-carbonitrile
|
MDL No. : | MFCD00052343 |
InChI Key : | WDHFCSOENXEMRC-UHFFFAOYSA-N |
Pubchem ID : | 2801166 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H317-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P272-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338+P310-P333+P313-P362-P403+P233-P405-P501 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 36.16 |
TPSA ? Topological Polar Surface Area: Calculated from |
75.59 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.18 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.09 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.61 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.83 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.62 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.93 |
Solubility | 1.82 mg/ml ; 0.0118 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.27 |
Solubility | 0.831 mg/ml ; 0.00537 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.98 |
Solubility | 1.62 mg/ml ; 0.0105 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 |
-6.47 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) |
1.83 |
* 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 |
---|---|---|
48% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 4h; | 0.25 g (1.61 mmol) of 4-amino-2-chloropyrimidine-5-carbonitrile, 0.31 g (2.10 mmol) of (1R)-1,2,3,4-tetrahydronaphthalen-1-amine and 0.67 g (4.85 mmol) of potassium carbonate in 3 ml of N,N-dimethylformamide are heated at 120 C. for 4 hours, the crude mixture is concentrated by evaporation under a high vacuum, the remaining crude mixture is absorbed on silica gel and purified by means of column chromatography using heptane/ethyl acetate as eluent. Following concentration by evaporation, 0.22 g of 4-amino-2-[(1R)-1,2,3,4-tetrahydronaphthalen-1-ylamino]pyrimidine-5-carbonitrile (m.p. 167.6 C.) is obtained (yield 48% at 95% purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; In 1,4-dioxane; at 0 - 20℃; for 2h; | Method E [0724] General conditions for the preparation of 2-amino-4-chloropyrimidine-5-carbonitrile: [0725] To a solution of 2,4-dichloropyrimidine-5-carbonitrile (E-1) (2.0 g, 11.5 mmol) in 1,4-dioxane (20 mL) at 0° C., ammonium hydroxide (28-30percent, 4.4 mL, 34.5 mmol) is added dropwise, and the resulting mixture is stirred while warming from 0° C. to RT for 2 h. Then, the mixture is partitioned between ethyl acetate (200 mL) and water (50 mL). The organic layer is washed with brine, dried over Na2SO4 and filtered. The filtrate is mixed with silica gel and then concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-100percent ethyl acetate/hexanes to afford the product ( E-2) (917 mg) and a mixture of (E-2) and (E-3). Additional (E-3) can be obtained from this mixture by a second column chromatographic purification. | |
917 mg | With ammonium hydroxide; In 1,4-dioxane; at 0 - 20℃; for 2h; | [00607] General conditions for the preparation of 2-amino-4-chloropyrimidine-5-carbonitrile:[00608] To a solution of 2,4-dichloropyrimidine-5-carbonitrile (E-1) (2.0 g, 11.5 mmol) in 1,4-dioxane (20 mL) at 0 °C, ammonium hydroxide (28-30percent, 4.4 mL, 34.5 mmol) is added dropwise, and the resulting mixture is stirred while warming from 0 °C to RT for 2 h. Then, the mixture is partitioned between ethyl acetate (200 mL) and water (50 mL). The organic layer is washed with brine, dried over Na2SO4 and filtered. The filtrate is mixed with silica gel and then concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0- 100percent ethyl acetate/hexanes to afford the product (E-2) (917 mg) and a mixture of (E-2) and (E-3). Additional (E-3) can be obtained from this mixture by a second column chromatographic purification. |
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