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Structure of 27757-86-4
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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. : | 27757-86-4 |
Formula : | C5H7NS |
M.W : | 113.18 |
SMILES Code : | NCC1=CSC=C1 |
MDL No. : | MFCD01529872 |
InChI Key : | DUDAKCCDHRNMDJ-UHFFFAOYSA-N |
Pubchem ID : | 2776381 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅲ |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 31.99 |
TPSA ? Topological Polar Surface Area: Calculated from |
54.26 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.43 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.46 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.18 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.29 |
Solubility | 5.75 mg/ml ; 0.0508 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.17 |
Solubility | 7.69 mg/ml ; 0.0679 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.65 |
Solubility | 2.52 mg/ml ; 0.0222 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 |
-6.66 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) |
1.75 |
* 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 bis(isopropyl)ethylamine; In propan-1-ol; at 80℃; for 6h; | A mixture of <strong>[27757-86-4]3-(aminomethyl)thiophene</strong> (0.25 mL, 2.5 mmol), 6-chloropurine ribofuranoside (143 mg, 0.5 mmol), and diisopropylethylamine (2 mL, 12 mmol) in 1-propanol (25 mL) was heated at 80 C for 6 h. The mixture was concentrated by rotary evaporation, and recrystallized from MeOH to yield the desired product JMF3461 (136 mg, 75% yield). The purity of product was 99% as shown by HPLC on an HC-C18 column (Agilent, 4.6 chi 250 mm, 5 mutaueta) with elution of gradients of 50% aqueous MeOH. C15Hi7504S; yellow powder; mp 134.3-135.1 C; [a]2D= -58.6 (DMSO, c = 1.0); TLC (2-propanol/hexane, (2:3)) R = 0.33; 1H NMR (DMS0-4s, 400 MHz) 6 8.36 (2 H, br s), 8.22 (1 H, s), 7.43 (1 H, dd, J= 3, 5 Hz), 7.28 (1 H, d, J= 1.6 Hz), 7.09 (1 H, d, J= 4.8 Hz), 5.88 (1 H, d, J = 6.4 Hz), 5.43 (1 H, d, J= 6.0 Hz), 5.38 (1 H, q, J= 4.6 Hz), 5.17 (1 H, d, J= 4.4 Hz), 4.69 (2 H, s), 4.63^1.16 (1 H, m), 4.14-4.13 (1 H, m), 3.97-3.95 (1 H, m), 3.69-3.64 (1 H, m), 3.57-3.52 (1 H, m),13C NMR (DMSO-i/<s, 100 MHz) delta 154.4, 152.3, 148.5, 140.8, 139.9, 127.9, 125.1, 120.0, 1 19.8, 87.9, 85.9, 73.5, 70.7, 61.7, 42.9; ESI-MS calcd for CuH^NjC^S: 364.1080, found: m/z 364.1079 [M + H]+. |
75% | With N-ethyl-N,N-diisopropylamine; In propan-1-ol; at 80℃; for 6h; | <strong>[27757-86-4]3-(aminomethyl)thiophene</strong> (0.25 mL, 2.5 mmol) '6-chloropurine nucleofuranoside (143 mg, 0.5 mmol), and diisopropylethylamine (2 mL, 12 mmol) The 1-propanol (25 mL) mixture was heated at 80 C for 6 hours. The mixture was concentrated by rotary evaporation and recrystallized from EtOAc to give the desired product JMF 3461 ( 136 mg, 75% yield). The purity of the product is 99%, |
With triethylamine; In propan-1-ol; at 70℃; for 8h; | First step, hydroxyamine hydrochloride (874 mg) and NaOAc (1.18 g) were added to a solution of 3-thiophenecarbaldehyde (800 mg) in EtOH (50 ml). The reaction mixture was stirred at room temperature for 6 h. EtOH was removed under reduced pressure. H2O (40 ml) was added to the residue, and extracted with EtOAc (3 × 40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield 3-thiophenecarbaldehyde oxime (722 mg) as a pale yellowish solid. Second step, 3-thiophenecarbaldehyde oxime (722 mg) and zinc dust (2.23 g) in HOAc (5 ml) was stirred at room temperature for 6 h. The reaction solution was filtered to remove the excess zinc dust and ZnOAc residue, and the filtrate was concentrated to yield 3-thiopheneylmethanamine (323 mg) as a yellowish oil. Third step, a mixture of 3-thiopheneylmethanamine (158 mg), 6-chloropurine riboside (200 mg) and triethylamine (3 ml) in PrOH (60ml) was heated to 70C and reacted for 8 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (20 : 1) to yield N6-(3-thiopheneylmethyl)-adenosine(150 mg) as a white solid: positive ESIMS m/z 364[M + H]+, 386[M + Na]+ and 402 [M + K]+; negative ESIMS m/z 362[M - H]-; 1H NMR (300MHz, DMSO-d6): the adenosine moiety delta 8.36 (2H, s, -NH, H-2), 8.22 (1H, s, H-8), 5.88 (1H, d, 6.0Hz, H-1), 5.43 (1H, d, 6.0Hz, -OH), 5.38 (1H, m, -OH), 5.17 (1H, d, 4.5Hz, -OH), 4.60 (1H, m, H-2'), 4.13 (1H, m, H-3'), 3.95 (1H, m, H-4'), 3.70-3.64 (1H, m, H-5a'), 3.58 (1H, m, H-5b'); the 3-thiopheneylmethyl moiety delta 7.43 (1H, dd, 4.8Hz, 3.0Hz, H-5"), 7.28 (1H, brs, H-2"), 7.08 (1H, dd, 4.8Hz, 0.9Hz, H-4"), 4.68 (2H, brs, H-7"); 13C NMR (75MHz, DMSO-d6): the adenosine moiety delta 154.4 (s, C-6), 152.5 (d, C-2), 148.6 (s, C-4), 140.9 (d, C-8), 119.9 (s, C-5), 88.1 (d, C-1), 86.1 (d, C-4'), 73.7 (d, C-2'), 70.8 (d, C-3'), 61.8 (t, C-5'); the 3-thiopheneylmethyl moiety delta 140.1 (s, C-3"), 127.7 (d, C-4"), 126.2 (d, C-5"), 121.8 (d, C-2"), 39.5 (t, C-6)omicron |
150 mg | With triethylamine; In propan-1-ol; at 70℃; for 8h; | Third step, a mixture of 3-thiopheneylmethanamine (158 mg), 6-chloropurine riboside (200 mg) and triethylamine (3 ml) in PrOH (60 ml) was heated to 70 C. and reacted for 8 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (20:1) to yield N6-(3-thiopheneylmethyl)-adenosine (150 mg) as a white solid: positive ESIMS m/z 364[M+H]+, 386[M+Na]+ and 402 [M+K]+; negative ESIMS m/z 362[M-H]-; 1H NMR (300 MHz, DMSO-d6): the adenosine moiety delta 8.36 (2H, s, -NH, H-2), 8.22 (1H, s, H-8), 5.88 (1H, d, 6.0 Hz, H-1'), 5.43 (1H, d, 6.0 Hz, -OH), 5.38 (1H, m, -OH), 5.17 (1H, d, 4.5 Hz, -OH), 4.60 (1H, m, H-2'), 4.13 (1H, m, H-3'), 3.95 (1H, m, H-4'), 3.70-3.64 (1H, m, H-5a'), 3.58 (1H, m, H-5b'); the 3-thiopheneylmethyl moiety delta 7.43 (1H, dd, 4.8 Hz, 3.0 Hz, H-5"), 7.28 (1H, brs, H-2"), 7.08 (1H, dd, 4.8 Hz, 0.9 Hz, H-4"), 4.68 (2H, brs, H-7"); 13C NMR (75 MHz, DMSO-d6): the adenosine moiety delta 154.4 (s, C-6), 152.5 (d, C-2), 148.6 (s, C-4), 140.9 (d, C-8), 119.9 (s, C-5), 88.1 (d, C-1'), 86.1 (d, C-4'), 73.7 (d, C-2'), 70.8 (d, C-3'), 61.8 (t, C-5'); the 3-thiopheneylmethyl moiety delta 140.1 (s, C-3"), 127.7 (d, C-4"), 126.2 (d, C-5"), 121.8 (d, C-2"), 39.5 (t, C-6). |
150 mg | With triethylamine; In propan-1-ol; at 70℃; for 8h; | 158 mg of 3-thiophene methylamine was taken and dissolved in propanol (60 mL). To a solution of 6-chloropurine nucleoside (200 mg) and triethylamine (3 mL)The mixture was heated to 70 C., reacted for 8 hours, and the solvent was recovered with a reaction solution. Chloroform-methanol (20: 1) separated by silica gel column chromatography, To obtain 150 mg of N6-(3-thiophenemethyl)adenosine as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium sulfate; In tetrahydrofuran; | Synthesis of thiophen-3-yl-methylamine (Scheme V, Compound 12) Add a solution of thiophene-3-carbaldehyde oxime (97.2 g, 0.9 mol) in tetrahydrofuran (500 mL) to cold (18C) lithium aluminum hydride bis tetrahydrofuran complex (1.0 M solution in tetrahydrofuran, 1.75 L), in a dropwise fashion, over ~0.5 hours. Alternatively, toluene may be used as the solvent. Gas evolution is observed and the addition temperature is maintained at 18-25C. Let reaction mixture stir overnight. Cool reaction mixture and carefully quench with water (252 mL), over ~40 minutes. Add additional tetrahydrofuran (300 mL) to thin out the reaction mixture upon quenching and stir at room temperature for 3 hours. Add sodium sulfate (250 g), filter through celite, and concentrate (50-60C/30 torr) reaction mixture to give the title compound as an oil (81.5 g, 82% Yield: 1H NMR (CDCl3, 200MHz) delta 1.5-1.8 (br s, 2H), 3.9 (s, 2H), 7.04 (d, 1H), 7.1 (d, 1H), 7.3 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; for 0.5h;Product distribution / selectivity; | 4 mmol C-Thiophen-3-yl-methylamine and 1 mmol (2-Oxo-ethyl)-carbamic acid tert-butyl ester were added in 5 ml MeOH (dry). After 30 min the 1 mmol 2-Chloro-4-fluoro-1-[isocyano-(toluene-4-sulfonyl)-methyl]-benzene was added. The reaction was heated to 40 C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods.; C-<strong>[27757-86-4]thiophen-3-yl-methylamine</strong> (4 mmol) and (2-oxo-ethyl)-carbamic acid tert-butyl ester (1 mmol) were added to methanol (5 ml, dry). After 30 min 2,4-dichloro-1-[isocyano-(toluene-4-sulfonyl)-methyl]-benzene (1 mmol) was added. The reaction was heated to 40 C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In methanol; 1,1-dichloroethane; ethanol; dichloromethane; | Scheme III, Step O: To a solution of (R)-6-fluoro-3-(3-oxiranylmethoxy-phenyl)-benzo[d]isoxazole (150 mg, 526 mmol) in dichloroethane (2 mL) add <strong>[27757-86-4]thiophen-3-yl-methylamine</strong> (119 mg, 1.05 mmol) (Table No.1, SM 9) and ethanol (2 mL) and heat at 85C for 10 hours. Cool reaction mixture at-25C and concentrate. Purify the compound on a Waters Sep-Pak silica cartridge using solvent mixtures anywhere from 1% to 10% methanol in dichloromethane to give the title compound (113.0 mg, 68% Yield). Purity by LC/MS=~100%, [M+H]+=399. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Scheme III, Step R: The title compound is prepared from a mixture of 3-[4-(3-bromo-propoxy)-phenyl]-6-fluoro-benzo[d]isoxazole, <strong>[27757-86-4]thiophen-3-yl-methylamine</strong> (Table No. 1, SM 9), potassium carbonate and acetonitrile essentially as described above in Example 10 except that the compound is recrystallized from methanol. Microanalysis (C, H, N) is consistent with the final, desired compound. mp=262-265C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; | Scheme III, Step O: The title compound is prepared from a mixture of 2-(4-benzo[b]thiophen-3-yl-phenoxymethyl)-oxirane, <strong>[27757-86-4]thiophen-3-yl-methylamine</strong> (Table No.1, SM 9) and ethanol essentially as described above in Example 96. Purity by LC/MS=99%, [M+H]+=396. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; ethyl acetate; | Scheme III, Step R: The title compound is prepared from 3-[4-(3-bromo-propoxy)-phenyl]-benzo[b]thiophene, C-thiophene-3-yl-methylamine (Table No. 1, SM 9), potassium carbonate and acetonitrile essentially as described above in Example 118 except that the column chromatography is performed with a graded solvent mixture from 100% ethyl acetate to 10% methanol in ethyl acetate. Purity by LC/MS=99%, [M+H]+ = 380. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 39 3-(2,3-dichlorophenyl)-4-(thien-3-ylmethyl)-4H-1,2,4-triazole The title compound was prepared as its trifluoroacetic acid salt using the procedure as described in Example 1D substituting thien-3-ylmethylamine for benzylamine. MS (DCI/NH3) m/z 310 (M+H)+; 1H NMR (CDCl3) delta 5.07 (s, 2H), 6.81 (dd, 1H), 7.05 (d, 1H), 7.31-7.34 (m, 3H), 7.66 (dd, 1H), 8.46 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80%Chromat. | With borane-ammonia complex; C15H30Cl2CoN3P; In hexane; at 50℃; for 16h;Inert atmosphere; Schlenk technique; | General procedure: Under the protection of argon, the complex represented by the catalyst formula 1 (0.5-1 mol%), ammonia borane (0.6 _1.5 equiv), benzonitrile (0.5 mmol) and n-hexane (2 mL) were sequentially added to a 25 mL shrek bottle containing a magnetic stirrer and reacted at 25-50C for 16 hours. After the reaction was completed, the reaction mixture was diluted with 5 mL of methanol. The reaction product was quantified by GC using biphenyl as an internal standard. |
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