Structure of 5-Thiazolemethanol
CAS No.: 38585-74-9
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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. : | 38585-74-9 |
Formula : | C4H5NOS |
M.W : | 115.15 |
SMILES Code : | C1=C(SC=N1)CO |
MDL No. : | MFCD04115732 |
InChI Key : | WKBQQWDVVHGWDB-UHFFFAOYSA-N |
Pubchem ID : | 2763216 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H318-H412 |
Precautionary Statements: | P501-P273-P280-P305+P351+P338+P310 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 28.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
61.36 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.1 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.48 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.08 |
Solubility | 9.59 mg/ml ; 0.0833 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.94 |
Solubility | 13.1 mg/ml ; 0.114 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.07 |
Solubility | 9.85 mg/ml ; 0.0855 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 |
-6.93 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 |
2.0 |
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) |
2.01 |
* 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 |
---|---|---|
75% | With sodium hydroxide In tetrahydrofuran; methanol; chloroform; water; ethyl acetate | C. 5-(Hydroxymethyl)thiazole To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (2.89 g, 76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol) in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15percent NaOH, and 8.7 mL of water. The solid salts were filtered, and the filtrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 minutes. The resulting mixture was filtered, and the two filtrates were combined, dried over Na2 SO4, and concentrated in vacuo. The product was purified by silica gel chromatography eluding sequentially with 0percent -2percent -4percent methanol in chloroform, to provide the desired compound, Rf-0.3 (4percent methanol in chloroform), which solidified upon standing in 75percent yield. NMR (CDCl3) δ4.92 (s, 2H), 7.78 (s, 1H), 8.77 (s, 1H). Mass spectrum: (M+H)+ =116. |
75% | With sodium hydroxide In tetrahydrofuran; methanol; chloroform; water; ethyl acetate | P. 5-(Hydroxymethyl)thiazole To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol) in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15percent NaOH, and 8.7 mL of water. The solid salts were filtered, and the flitrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 min. The resulting mixture was filtered, and the two filtrates were combined, dried over Na2 SO4, and concentrated in vacuo. The product was purified by silica gel chromatography eluding sequentially with 0percent -2percent-4percent methanol in chloroform, to provide the desired compound, Rf=0.3 (4percent methanol in chloroform), which solidified upon standing in 75percent yield. NMR (CDCl3)δ4.92 (s, 2H), 7.78 (s, 1H), 8.77 (s, 1H). Mass spectrum: (M+H)+ =116. |
75% | With sodium hydroxide In tetrahydrofuran; methanol; chloroform; water; ethyl acetate | K. 5-(Hydroxymethyl)thiazole To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol) in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15percent NaOH, and 8.7 mL of water. The solid salts were filtered, and the filtrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 min. The resulting mixture was filtered, and the two filtrates were combined, dried over Na2 SO4, and concentrated in vacuo. The product was purified by silica gel chromatography eluding sequentially with 0percent - 2percent - 4percent methanol in chloroform, to provide the desired compound, Rf=0.3 (4percent methanol in chloroform), which solidified upon standing in 75percent yield. NMR (CDCl3) δ4.92 (s, 2H), 7.78 (s, 1 H), 8.77 (s, 1H). Mass spectrum: (M+H)+ =116. |
75% | With sodium hydroxide In tetrahydrofuran; methanol; chloroform; water; ethyl acetate | K. 5-(Hydroxymethyl)thiazole. To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol) in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15percent NaOH, and 8.7 mL of water. The solid salts were filtered, and the filtrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 min. The resulting mixture was filtered, and the two filtrates were combined, dried over Na2 SO4, and concentrated in vacuo. The product was purified by silica gel chromatography eluding sequentially with 0percent-2percent-4percent methanol in chloroform, to provide the desired compound, Rf=0.3 (4percent methanol in chloroform), which solidified upon standing in 75percent yield. NMR (CDCl3) δ4.92 (s, 2H), 7.78 (s, 1H), 8.77 (s, 1H). Mass spectrum: (M+H)+ =116. |
75% | With sodium hydroxide In tetrahydrofuran; methanol; chloroform; water; ethyl acetate | D. 5-(Hydroxymethyl)thiazole To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol)in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15percent NaOH, and 8.7 mL of water. The solid salts were filtered, and the filtrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 min. The resulting mixture was filtered, and the two flitrates were combined, dried over Na2 SO4, and concentrated in vacuo. The product was purified by silica gel chromatography eluding sequentially with 0percent-2percent-4percent methanol in chloroform, to provide the desired compound, Rf=0.3 (4percent methanol in chloroform), which solidified upon standing in 75percent yield. NMR (CDCl3) δ4.92 (s, 2 H), 7.78 (s, 1 H), 8.77 (s, 1 H). Mass spectrum: (M+H)+ =116. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at 0℃; for 1 h; Stage #2: With sodium hydroxide In water at 0℃; for 0.5 h; |
A mixture of 0. 54 g of g-4 and 10ml tetrahydrofurane (THF) was stirred at 0°C under a nitrogen atmosphere. The mixture of 0. 16g of lithium aluminium hydride and 5ml of ether was added drop wise. After lhour at 0°C water and 20percent sodium hydroxide were added, and stirred during 30 minutes. The mixture was filtered over decalite and the solvent was removed by azeotropique distillation with toluene yielding 0.3g (69percent) of thiazol-5-yl-methanol (g-5). |
A205959 [131748-97-5]
(2-(Trifluoromethyl)thiazol-5-yl)methanol
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