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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Structure of 407-97-6
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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. : | 407-97-6 |
Formula : | C5H10BrF |
M.W : | 169.04 |
SMILES Code : | FCCCCCBr |
MDL No. : | MFCD01709395 |
InChI Key : | GMYIZICPHREVDH-UHFFFAOYSA-N |
Pubchem ID : | 120236 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 34.07 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.94 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.43 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.14 |
Solubility | 1.24 mg/ml ; 0.00731 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.54 mg/ml ; 0.00908 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.03 |
Solubility | 0.158 mg/ml ; 0.000935 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-5.63 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 |
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) |
2.48 |
* 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 |
---|---|---|
60% | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; | To a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]-2-hydroxyphenyl}-1H-1,2,3-triazole-4-carboxamide (0.16 g) obtained in Example 139 in DMF (5 ml) were added <strong>[407-97-6]1-bromo-5-fluoropentane</strong> (0.11 g) and potassium carbonate (0.07 g), and the mixture was stirred at 50°C overnight. The reaction mixture was allowed to cool to room temperature, and water was added to the reaction mixture. The deposited precipitate was collected by filtration, washed with water, and recrystallized from ethanol-water to give the title compound as a pale-brown powder (0.12 g, 60percent). NMR (CDCl3) delta: 0.68-0.72 (2H, m), 0.86-0.93 (2H, m), 1.29 (3H, t, J = 7.2), 1.52-1.90 (7H, m), 2.93-2.96 (2H, m), 3.51-3.58 (2H, m), 4.19 (2H, t, J = 6.6), 4.45 (2H, td, J = 6.0, 47.3), 6.15 (1H, brs), 7.36 (1H, dd, J = 1.7, 8.3), 7.65 (1H, d, J = 1.7), 7.88 (1H, d, J = 8.3), 8.68 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; | To a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]-2-hydroxyphenyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide (0.17 g) obtained in Example 141 in DMF (5 ml) were added <strong>[407-97-6]1-bromo-5-fluoropentane</strong> (0.11 g) and potassium carbonate (0.07 g), and the mixture was stirred at 50°C overnight. The reaction mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate-hexane (2:1). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column (ethyl acetate) to give the title compound as a pale-yellow amorphous substance (0.16 g, 77percent). NMR (CDCl3) delta: 0.65-0.70 (2H, m), 0.85-0.91 (2H, m), 1.29 (3H, t, J = 7.2), 1.35-1.43 (2H, m), 1.57-1.76 (4H, m), 2.46 (3H, s), 2.87-2.95 (1H, m), 3.49-3.59 (2H, m), 4.07 (2H, t, J = 6.6), 4.38 (2H, td, J = 6.0, 47.3), 6.19 (1H, brs), 7.31-7.41 (3H, m), 7.61 (1H, d, J = 1.3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 60℃; | To a solution of tert-butyl [[(R)-1-HYDROXY-4-(4-HYDROXY-PHENYL)-2-METHYL-BUT-2-YL]-CARBAMATE] (200 mg, 0.68 mmol, Ex. [1B)] and [1-BROMO-5-FLUOROPENTANE] (172 mg, 1.02 mmol, 1.5 eq. ) in anhydrous DMF (2.5 ml) is added water free caesium carbonate (331 mg, 1.02 mmol, 1.5 eq. ). The suspension obtained is stirred over night protected from moisture at [60°C.] After cooling to RT the solids are filtered off and rinsed with DMF [(2 X 1 ML).] The combined filtrates are evaporated in a high vacuum to give a dark orange syrup. Purification by flash chromatography [(FLASHMASTER] ll, MTBE/hexanes gradient as disclosed in Ex 1a)) gives colorless crystals: mp. [91-93°C,] ESI+ MS: m/z = 406 (MNa+), 384 (MH+), 328 [(MH+-TBU),] 1H-NMR (400 MHz, [CDCI3)] : [8] 1.23 (s, 3H, 2-Me), 1.46 (s, 9H, tBu), 1.60 (cm, 2H, [3APOS;-CH2),] 1.74 (cm, [1H, 3-CHALPHA;), ] 1.77-1. 90 (m, 4H, 2'- 4'-CH2), 2.03 (cm, 1 H, 3-CHp), 2.48-2. 69 (m, 2H, 4-CH2), 3.64 (br d, [1H, 2J=11.] 3, [1-CHALPHA;), ] 3.72 (br d, 1H, 2J=11. 9, 1-CHp), 3.96 (t, 2H, J=7.1, 1'-OCH2), 4.03 (br, [1H,] OH), 4.48 (dt, 2H, [2JH, F=47.] 8, 3JH, [H=7. 2,] 5'-CH2F), 4.62 (br s, [1H,] NH), 6.80 [(APOS;DAPOS;,] 2H, [J=10.] 1, ArH), 7.08 [(APOS;DAPOS;,] J=10. 3, [ARH).] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With potassium carbonate; In acetonitrile; at 90℃; | General procedure: To a solution of 2 (0.3mmol) in CH3CN (2mL) was added K2CO3 (0.9mmol) and fluoroalkoxy bromide (0.7mmol). The reaction was heated to 90C for 2-5h (monitored by HPLC). Upon completion, the reaction was cooled and the liquid was decanted from solids. Residual solids were washed twice with DCM (2mL), organic solvents were combined and concentrated. Following silica gel chromatography using hexane and ethyl acetate as eluent, white solids were isolated upon evaporation of solvent. 1=82mg, 81%, mp: 102-103C, 1H NMR (CDCl3, 400MHz) delta ppm: 8.40 (d, J=8.8Hz, 1H), 6.92-6.87 (m, 2H), 4.93-4.89 (m, 1H), 4.67 (dt, J=5.7Hz, JHF=47.0, 2H), 4.27-4.08 (m, 4H), 3.74 (dd, J=9.1, 4.2, 1H), 3.64 (dd, J=9.1, 4.0Hz, 1H), 2.22 (dp, J=26.1, 5.9Hz, 2H). HRMS C15H18N2O5F [M+H]+ observed 325.1195, calculated 325.1194. (R)-1 was prepared in a similar manner using (S)-2. 4=97mg, 96%, 1H NMR (CDCl3, 400MHz) delta ppm: 8.41 (d, J=10.0Hz, 1H), 6.91 (m, 2H), 4.93 (m, 1H), 4.56 (dt, J=7.2Hz, JHF=48Hz, 2H), 4.26 (t, J=8.0Hz, 1H), 4.12 (m, 3H), 3.71 (dq, J=4.2Hz, J=6.7, 2H), 3.46, (s, 3H), 1.88-2.02 (m, 4H). MS C16H20N5O5F [M+H]+ observed 339, calculated 339. 5=72mg, 71%, 1H NMR (CDCl3); 400MHz) delta: 8.41 (d, J=10.0Hz, 1H), 6.94 (m, 2H), 4.94 (m, 1H), 4.51 (dt, J=7.2Hz, JHF=48Hz, 2H), 4.26 (t, J=8.0Hz, 1H), 4.13 (dd, J=6.6Hz, 10.4Hz, 1H), 4.06 (t, J=6.6Hz) 3.70 (dq, J=4.2Hz, J=6.7, 2H), 3.46, (s, 3H), 1.74-1.95 (m, 4H), 1.6-1.7 (m, 2H). MS C20H22N2O5F [M+H]+ observed 353, calculated 353 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h; | (S) -N- (2,6-dimethylphenyl) piperidine-2-carboxamide (1a) (5.0 g, 21.52 mmol)1-bromo-3-fluoro-pentane (4.37 g, 25.9 mmol)Potassium carbonate (4.46 g, 32.3 mmol),50 ml of N, N-dimethylformamide was added to the reaction flask,80 stirring 3h,The reaction was stopped;Add an equal volume of ice water to stir to precipitate a white solid which was filtered and the solid was washed with ice water (20 ml x 4) and dried to give a white solid;The white solid was dissolved in 30 ml of ethyl acetate,Add 4M hydrochloric acid to no longer white solid precipitation,filter,The solid was washed with ethyl acetate,(S) -N- (2,6-diethylphenyl) -1- (5-fluoropentyl) piperidine-2-carboxamide hydrochloride (37) (6.11 g 79.2percent) was dried. |