Structure of 259654-73-4
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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. : | 259654-73-4 |
Formula : | C7H10N2O2S |
M.W : | 186.23 |
SMILES Code : | O=C(OC)CC1=C(C)SC(N)=N1 |
MDL No. : | MFCD00662517 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
93.45 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.76 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.02 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.63 |
Solubility | 4.39 mg/ml ; 0.0236 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.37 |
Solubility | 0.785 mg/ml ; 0.00422 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.8 |
Solubility | 2.92 mg/ml ; 0.0157 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 |
-6.85 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) |
2.44 |
* 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 |
---|---|---|
63% | In toluene; at 100℃; for 1h; | To a solution of bromide from Step 1 (18 g, 86 [MMOL)] in toluene (100 mL) was added thiourea (10.5 g, 138 [MMOL).] The reaction mixture was heated to [100C] for 1 h, cooled to rt, and the solvent removed under reduced pressure. The residue was dissolved in [CH2CI2] (100 mL), a saturated solution of [NAHC03] (75 mL) was added, and the mixture was vigorously stirred for 10 minutes. The organic layer was separated, dried [(NA2SO4),] filtered, and concentrated under reduced pressure. The residue was then recrystallized from [CH2CI2/HEXANES] to provide the product (10 g, 63%) as a white solid. [(C7H10N202S)] : LC-MS, RT 0.76 min, (M+H) [+] 187.0 ;'H NMR [(CDCI3)] : [6] 2.23 (s, 3H), 3.70 (s, 2H), 3.75 (s, 3H), 4.83-4. 95 (broad s, 2H). |
63% | In toluene; at 100℃; for 1h; | To a solution of bromide of Example 170 (18 g, 86 mmol) in toluene (100 mL) was added thiourea (10.5 g, 138 mmol). The reaction mixture was heated to 100 C. for 1 hour, cooled to rt, and the solvent removed under reduced pressure. The residue was dissolved with CH2Cl2 (100 mL), a saturated solution NaHCO3 (75 mL) added, and the mixture was vigorously stirred for 10 minutes. The organic layer was separated, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then recrystallized from CH2Cl2/hexanes to provide the product (10 g, 63%) as a white solid. (C7H10N2O2S): LC-MS, RT 0.76 min, M+H 187.0; 1H NMR (CDCl3): delta 2.23 (s, 3H), 3.70 (s, 2H), 3.75 (s, 3H), 4.83-4.95 (broad s, 2H). |
63% | In toluene; at 100℃; for 1h; | To a solution of bromide of Example 170 (18 g, 86 mmol) in toluene (100 mL) was added thiourea (10.5 g, 138 mmol). The reaction mixture was heated to 100 C. for 1 hour, cooled to rt, and the solvent removed under reduced pressure. The residue was dissolved with CH2Cl2 (100 mL), a saturated solution NaHCO3 (75 mL) added, and the mixture was vigorously stirred for 10 minutes. The organic layer was separated, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then recrystallized from CH2Cl2/hexanes to provide the product (10 g, 63%) as a white solid. (C7H10N2O2S): LC-MS, RT 0.76 min, M+H 187.0; 1H NMR (CDCl3): delta 2.23 (s, 3H), 3.70 (s, 2H), 3.75 (s, 3H), 4.83-4.95 (broad s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | To a solution of the compound prepared in Step 2 (5.00 g, 26.8 [MMOL)] and DMAP (32 mg, 0.26 [MMOL)] in [CH2C12] (150 mL) was added BOC2O (7.00 g, 32.2 [MMOL).] After 4 h, additional quantities of [BOC20] (7.00 g, 32.2 [MMOL)] and Et3N (7.50 mL, 53.6 [MMOL)] were added. The reaction mixture was stirred at rt for 18 h, then a saturated solution of [NH4CI] (100 mL) was added and the reaction was stirred for 15 minutes. The layers were separated, dried [(NA2SO4),] filtered, and concentrated under reduced pressure. The residue was passed through a short plug of silica gel to yield a mixture of the corresponding mono-and di-carbamate. This mixture was dissolved in [MEOH] (40 mL), and a [1 N SOLUTION] of [NAOH] (20 mL) was added. The solution was stirred for 90 minutes, the methanol removed under reduced pressure and the residue was washed with [ET20] (2 x 10 mL). The aqueous layer was acidified to [PH # 4 ] using 1 N HCI, extracted with CH2CI2 (2 x 50 mL), and the combined organic layers dried [(NA2SO4),] filtered and concentrated under reduced pressure to afford the desired product as a yellow solid (4. [4 G,] 60%). (C11H16N2O4S) : LC-MS, [RT 2.] 39 min, (M+H) [+ 272.] 9 ;'H NMR [(CDCI3)] : [6] 1.51 (s, 9H), 2.32 (s, 3H), [3.] 61 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Example 171 Preparation of Methyl (2-amino-5-methyl-1,3-thiazol-4-yl)acetate To a solution of bromide of Example 170 (18 g, 86 mmol) in toluene (100 mL) was added thiourea (10.5 g, 138 mmol). The reaction mixture was heated to 100 C. for 1 hour, cooled to rt, and the solvent removed under reduced pressure. The residue was dissolved with CH2Cl2 (100 mL), a saturated solution NaHCO3 (75 mL) added, and the mixture was vigorously stirred for 10 minutes. The organic layer was separated, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then recrystallized from CH2Cl2/hexanes to provide the product (10 g, 63%) as a white solid. (C7H10N2O2S): LC-MS, RT 0.76 min, M+H 187.0; 1H NMR (CDCl3): delta 2.23 (s, 3H), 3.70 (s, 2H), 3.75 (s, 3H), 4.83-4.95 (broad s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at -20 - 15℃; for 2h; | To a solution of CuBr2 (4.03 g, 18.1 mmol) and t-butyl nitrite (2.82 mL, 23.8 mmol) in MeCN (210 mL) was added the compound of Example 170 (2.95 g, 15.9 mmol) at -20 C. The reaction mixture was slowly warmed to 15 C., at which point the evolution of N2 was observed. After stirring for an additional 2 hours at 15 C., the reaction mixture was diluted with Et2O (400 mL) and washed with a 10% solution of HCl (200 mL). The solvent layers were separated, the aqueous re-extracted with Et2O (2*300 mL), and the combined organic layers dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was then purified by silica gel flash chromatography (98:2, hexanes/EtOAc) to afford bromide Example 172 (1.6 g, 40%) as a colorless oil that solidifies upon standing. (C7H8BrNO2S): LC-MS, RT 2.56 min., M+H 250.3; 1H NMR (CDCl3): delta 2.26 (s, 3H), 3.60 (s, 2H), 3.61 (s, 3H). |
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