Structure of 4-Aminoindan
CAS No.: 32202-61-2
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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. : | 32202-61-2 |
Formula : | C9H11N |
M.W : | 133.19 |
SMILES Code : | NC1=C2CCCC2=CC=C1 |
MDL No. : | MFCD00082598 |
InChI Key : | RXTJLDXSGNEJIT-UHFFFAOYSA-N |
Pubchem ID : | 122569 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.77 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.41 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.42 |
Solubility | 0.506 mg/ml ; 0.0038 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.26 |
Solubility | 0.739 mg/ml ; 0.00555 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.83 |
Solubility | 0.195 mg/ml ; 0.00147 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 |
-5.64 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) |
1.34 |
* 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 |
---|---|---|
86% | With hydrogen;palladium 10% on activated carbon; In ethanol; under 2585.81 Torr; for 1h; | Intermediate 8: 4-aminoindane In a 500 mL Parr shaker vessel, 4-nitroindane (10 g, 61 mmol) was dissolved in 50 mL ethanol. A slurry of 10% Pd/C (1 g) in ethanol was added. The mixture was then placed on a Parr shaker under a hydrogen atmosphere (50 psi) for 1 hour, at which point t.l.c. (20% ethyl acetate in hexanes) showed that all the starting material had disappeared. To work up the reaction, the mixture was filtered twice through Celite, washing with a large amount of ethanol, and once through filter paper. The ethanol was evaporated under reduced pressure, and the crude product purified by flash chromatography over silica gel (10% ethyl acetate in hexanes) to give 8 as a viscous, faintly colored oil (7.04 g, 86% yield): 1H NMR (400 MHz, DMSO-D6) delta 1.95 (m, 2H) 2.61 (t, J=7.3 Hz, 2H) 2.76 (t, J=7.5 Hz, 2H) 4.77 (s, 2H) 6.36 (d, J=7.8 Hz, 1H) 6.42 (d, J=6.8 Hz, 1H) 6.80 (t, J=7.6 Hz, 1H). |
86% | With hydrogen;palladium 10% on activated carbon; In ethanol; under 2585.81 Torr; for 1h; | In a 500 mL Parr shaker vessel, 4-nitroindane (10 g, 61 mmol) was dissolved in 50 mL ethanol. A slurry of 10% Pd/C (1 g) in ethanol was added. The mixture was then placed on a Parr shaker under a hydrogen atmosphere (50 psi) for 1 hour, at which point t.l.c. (20% ethyl acetate in hexanes) showed that all the starting material had disappeared. To work up the reaction, the mixture was filtered twice through Celite, washing with a large amount of ethanol, and once through filter paper. The ethanol was evaporated under reduced pressure, and the crude product purified by flash chromatography over silica gel (10% ethyl acetate in hexanes) to give 8 as a viscous, faintly colored oil (7.04 g, 86% yield): 1H NMR (400 MHz, DMSO-D6) delta 1.95 (m, 2H) 2.61 (t, J=7.3 Hz, 2H) 2.76 (t, J=7.5 Hz, 2H) 4.77 (s, 2H) 6.36 (d, J=7.8 Hz, 1H) 6.42 (d, J=6.8 Hz, 1H) 6.80 (t, J=7.6 Hz, 1H). |
43% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 2585.81 Torr; for 12h;Inert atmosphere; | To a solution of 4-nitro-2,3-dihydro-1H-indene g, 337.07 mmol, 1 eq) in MeOH(500 mL) was added Pd/C ( g, 10% purity) under N2. The suspension was degassed invacuo and purged with H2 several times. The reaction mixture was stirred at 20 C for12 hours under H2 (o psi), filtered and the filtrate was concentrated in vacuo. Theresidue was purified by column chromatography (Si02, PE: EtOAc = 1:0 to 100:4) to give the title compound (19.82 g, 43 % yield, 96.4 % purity on LCMS) as a brown oil. 1H NMR (CDC13): 6 7.01 (t, 1 H), 6.71 (d, 1 H), 6.i (d, 1 H), 3.57 (br 5, 2 H), 2.93 (t, 2H), 2.75 (t, 2 H) and 2.16-2.08 (m, 2 H).LCMS: m/z 134.2 (M+H) (ESI. |
With hydrogen;palladium on activated charcoal; In methanol; under 2585.81 Torr; for 14h; | 4-Nitro-indan (5.00 g, 30.70 mmol) was dissolved in methanol, and Pd/C (500 mg) was added. The resulting reaction mixture was hydrogenated at 50 psi for 14 hours. Filtration through celite and concentration afforded the title indan-4-yl-amine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(+-)-N-[7-(1-Butyryl-pyrrolidin-3-ylsulfamoyl)-indan-4-yl]-2-methyl-benzamide (H-71) The title compound was made following general procedure in Scheme 10, substituting <strong>[32202-61-2]indan-4-ylamine</strong> for 5,6,7,8-tetrahydro-naphthalen-1-yl amine and 3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester for 4-amino-piperidine-1-carboxylic acid tert-butyl ester 1H NMR (300 MHz, CDCl3) delta 8.22 (m, 1H), 7.76 (dd, 1H), 7.49 (m, 2H), 7.39 (m, 1H), 7.28 (m, 2H), 5.32 (dd, 1H), 3.80 (m, 1H), 3.40 (m, 5H), 2.88 (t, 2H); 2.52 (s, 3H), 2.20 (m, 6H), 1.90 (m, H), 1.60 (m, 2H), 0.84 (t, 3H); LC/MS m/z 470 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The title compounds were made following general procedure in Scheme 10, substituting <strong>[32202-61-2]indan-4-ylamine</strong> for 5,6,7,8-tetrahydro-naphthalen-1-ylamine and (+-)4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester. The diastereomers H-74 and H-75 were separated by flash column chromatography. H-74: 1H NMR (300 MHz, CDCl3) delta 8.25 (d, 1H), 7.79 (d, 1H), 7.50 (d, 1H), 7.30 (m, 8H), 4.46 (d, 1H), 3.42 (q, 2H), 3.35 (m, 4H), 2.82 (t, 2H), 2.54 (s, 3H), 2.23 (m, 2H), 2.28 (m, 2H), 1.87 (m, 1H), 1.56 (m, 3H), 0.83 (m, 3H); LC/MS m/z 518 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example SIXTEENbeta Procedure for the synthesis of 7-iodo-indan-1-one (Intermediate SIXTEENbeta3) "2 NHz o'0 v Method J S NaNO2, Kl S /z,, ---- y y Intermediate SIXTEENbeta 1 Intermediate Intermediate SIXTEENbeta3 SIXTEENbeta 2 Use of <strong>[32202-61-2]indan-4-ylamine</strong> (Intermediate SIXTEEN-beta-1) (commercially available from Aldrich) in Method J produced 7-amino-indan-1-one (Intermediate SIXTEENbeta-2). A mixture of [7-AMINO-INDAN-1-ONE] (Intermediate SIXTEENbeta-2) (1.44 g, 9.8 mmol) in water (11 mL), acetic acid (11 mL), and HCl (2.7 [ML)] was treated with a solution [OF NAN02] (0.75 g in 2.8 mL) at [0 C.] A solution of KI in water (1.76 g 10.4 mmol in 2.8 mL) was added and the mixture was heated to [60 C] for 1 h. The mixture was cooled and quenched with solid [NAHS03] followed by water. The product was extracted with CH2Cl2 (3x) and washed with sat. [NAHC03] and brine. The compound was purified by column chromatography on silica gel with 60 to 70% [CH2CL2] : hexane. [7-IODO-INDAN-L-ONE] (Intermediate SIXTEENbeta3) was isolated as a light yellow solid [(31%).] |