Structure of 4349-07-9
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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. : | 4349-07-9 |
Formula : | C4H3IN2O |
M.W : | 221.98 |
SMILES Code : | IC1=CN=CN=C1O |
MDL No. : | MFCD02666079 |
InChI Key : | SMIGOGPUTQXOKF-UHFFFAOYSA-N |
Pubchem ID : | 12356582 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
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 | 36.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.79 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.33 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.97 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.29 |
Solubility | 1.13 mg/ml ; 0.00508 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.38 |
Solubility | 9.28 mg/ml ; 0.0418 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.04 |
Solubility | 2.05 mg/ml ; 0.00923 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) |
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 |
-7.06 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 |
1.0 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) |
1.92 |
* 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 |
---|---|---|
88% | With oxalyl dichloride; N,N-dimethyl-formamide; In 1,2-dichloro-ethane; for 3h;Heating / reflux; | To a stirred solution containing 7.7 mL (99 MMOL) of DMF and 150 mL of DICHLOROETHANE at 0C was added 12.7 mL (144.6 MMOL) of OXALYL chloride slowly to control vigorous gas evolution. After the evolution of gas had ceased, 10.0 g of iodopyrimidone was added and the reaction mixture was heated at reflux for 3h, then cooled to room temperature and partitioned between water and DICHLOROMETHANE. The organic layers were dried over MGS04 and the solvent was removed under reduced pressure to give 9.6 g (88%) of the title COMPOUND. 1H-NMR (300 MHz, CDCI3) A 8. 89 (s, 1H) and 8.98 (s, 1H) ; ESIMS : 241.1 (M+H)+ |
83% | With oxalyl dichloride; In 1,2-dichloro-ethane; N,N-dimethyl-formamide; for 2h;Reflux; | Oxalyl chloride (1 .27 ml, 14.61 mmol) was added dropwise in 707 ml dimethylformamide and 20 ml dichloroethane. 5-lodopyrimidin-4(3/-/)-one ( 1 g, 4.55 mmol) was added and the reaction was heated at reflux for 2 h. The reaction mixture was dissolved in dichloromethane, washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure to give 0.91 g (83 % yield) of the title compound as a solid. Purity 100%.LRMS (m/z): 241 (M+1 )+ |
75.9% | With oxalyl dichloride; In 1,2-dichloro-ethane; N,N-dimethyl-formamide; at 0 - 85℃; for 4h; | N,N-dimethylformamide (3.9 mL, 27.0 mmol) was dissolved in 1,2-dichloroethane (90 mL) at 0 C, the reaction was stirred for 10 min, and oxalyl chloride (6.8 mL, 27.0 mmol) was added dropwise. ),After 20 minutes of dropwise addition, 5-iodopyrimidine-4(3H)one (5.0 g, 22.5 mmol) was added.The temperature was raised to 85 C for 4.0 h, and the reaction solution was concentrated.The residue was dissolved in dichloromethane (120 mL).The organic phase was washed with saturated brine (20 mL×2).Dry anhydrous sodium sulfate (20g),Filter and concentrate to give 4.1 g of a brown oil.The yield was 75.9%. The product was directly subjected to the next reaction without purification. |
With trichlorophosphate; In methanol; water; toluene; | Method V Preparation of 4-Chloro-5-iodopyrimidine 5-Iodo-4(3H)-pyrimidinone (1 eq.) was suspended in toluene to which was added POCl3 (2.0 eq.). The reaction mixture was heated to reflux for 3 hours, and then cooled and concentrated. The residue was suspended in water, adjusted to pH=7 by addition of 4N sodium hydroxide, and extracted with ethyl acetate. The organic extracts were washed with brine, dried (MgSO4), filtered and stripped to give a red oil. The crude product was dissolved in methanol and silica gel was added. Following concentration, the coated silica gel was loaded onto a plug of silica gel and elution with ethyl acetate/hexanes yielded the title compound. | |
With trichlorophosphate; In toluene; for 3h;Heating / reflux; | Method 0 Preparation of 4-Chloro-5-iodopyrimidine 5-Iodo-4(3H)-pyrimidinone (1 eq. ) was suspended in toluene to which was added POC13 (2.0 eq. ). The reaction mixture was heated to reflux for 3 hours, and then cooled and concentrated. The residue was suspended in water, adjusted to pH=7 by addition of 4N sodium hydroxide, and extracted with ethyl acetate. The organic extracts were washed with brine, dried (MgS04), filtered and stripped to give a red oil. The crude product was dissolved in methanol and silica gel was added. Following concentration, the coated silica gel was loaded onto a plug of silica gel and elution with ethyl acetate/hexanes yielded the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 2. Preparation of 4-chloro-5-iodopirnidine; A mixture of 5-iodopyrimidin-4-ol (14.9 g, 67.1 mmol) in phosphorous oxychloride (25.0 ml, 268 mmol) with a water-cooled reflux condenser fitted with a drying tube was heated to reflux in a 135 C. bath for 3 h. The purple solution was cooled until warm and poured onto ice with swirling. The ice-cold mixture was basified with 6N NaOH, with addition of ice to maintain the cool temperature. The resulting brown precipitate was collected by filtration, rinsed with water, and dried in vacuo to give 4-chloro-5-iodopyrimidine as an orange solid. MS m/z=241 [M+H]+. Calc'd for C4H2IClN2: 240.4. | ||
4 g | With oxalyl dichloride; In 1,2-dichloro-ethane; N,N-dimethyl-formamide; at 0 - 85℃; for 5h; | At 0 C,N,N-dimethylformamide (2.0 g, 27.0 mmol) was dissolved in 1,2-dichloroethane (60 mL), and stirred for 30 min.Oxalyl chloride (3.4 g, 27.0 mmol) was slowly added dropwise, and after the addition was completed,The solution is viscous,Add compound 4-hydroxy-5-iodopyrimidine(5g, 22.5mmol),The temperature was slowly raised to 85 C and the reaction was stirred for 5.0 h. concentrate,The residue was dissolved in dichloromethane (70 mL).The organic phase was washed once with distilled water (30 mL).Dry anhydrous sodium sulfate (12g), concentrated,4.0 g of a reddish brown oil was obtained, which was directly subjected to the next reaction. |
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