Structure of 85279-30-7
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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. : | 85279-30-7 |
Formula : | C8H9NO |
M.W : | 135.16 |
SMILES Code : | CC(=O)C1=NC=CC=C1C |
MDL No. : | MFCD08062668 |
InChI Key : | SYISHRLXIIZBHJ-UHFFFAOYSA-N |
Pubchem ID : | 13068669 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With potassium tert-butylate; In tetrahydrofuran; at -20 - 10℃; for 2h; | Dissolve 2-AMINO-4-CHLORONICOTINALDEHYDE (156 mg, 1.0 mmol) and 2-acetyl-3- methylpyridine (136 mg, 1.0 mmol) in anhydrous THF (5.0 mL) and cool it to-20C under N2 atmosphere. Add in portion t-BuOK (224 mg, 2.0 mmol) to the reaction mixture and stir the mixture at 10C for 2 hours. Concentrate the reaction mixture under vacuum, dilute the residue with water (10 mL), filter the solid, wash the solid with water and dry under high vacuum to afford the title product as a yellow colored solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
*2-Bromoacetyl-3-methylpyridine hydrobromide was prepared from <strong>[85279-30-7]2-acetyl-3-methylpyridine</strong> (T.A.Crabb et al., Org. Magn. Reson., 1982, 20 , 242) according to the procedure for preparing 2-bromoacetyl-4-methylpyridine hydrobromide described in step 5 of Example 1. 1H-NMR (DMSO-d6) delta: 8.56 (1H, d, J=3.6Hz), 7.84 (1H, d, J=7.7Hz), 7.56-7.60 (1H, m), 5.01 (2H, s), 4.01 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium hydride; In mineral oil; at 90℃; for 4h; | To a stirred solution of <strong>[85279-30-7]1-(3-methylpyridin-2-yl)ethanone</strong> (500 mg, 3.70 mmol, 1 eq) in diethyl carbonate (30 ml) was added NaH (60% in oil, 887.6 mg, 22.2 mmol, 6 eq) protionwise at 25 oC. The grey suspension was then stirred at 90 oC for 4 hours. Acetic acid (2.1 ml) in diethyl ether (21 ml) was added dropwise to quench the reaction. The resulting mixture was filtered through a pad of celite. The filtrate was concentrated and purified on silica gel (80 g) with a gradient of ethyl acetate in hexanes from 0 : 1 to 3 : 7 to give a dark brown oil (650 mg, 85%). 1H NMR (300 MHz, CDCl3): delta 8.52-8.46 (m, 1H), 7.63-7.59 (m, 1H), 7.35 (dd, J = 7.9, 4.5 Hz, 1H), 4.24-4.10 (m, 4H), 2.63 (s, 3H), 1.23 (t, J = 7.0 Hz, 3H); Calculated for C11H13NO3, 207.09; MS (ESI) (m/z) observed 208.2 (M + 1)+. |
85% | With sodium hydride; In mineral oil; at 25 - 90℃; for 4h; | To a stirred solution of <strong>[85279-30-7]1-(3-methylpyridin-2-yl)ethanone</strong> (500 mg, 3.70 mmol, 1 eq) in diethyl carbonate (30 ml) was added NaH (60% in oil, 887.6 mg, 22.2 mmol, 6 eq) protionwise at 25 C. The grey suspension was then stirred at 90 C for 4 hours. Acetic acid (2.1 ml) in diethyl ether (21 ml) was added dropwise to quench the reaction. The resulting mixture was filtered through a pad of celite. The filtrate was concentrated and purified on silica gel (80 g) with a gradient of ethyl acetae in hexances from 0 : 1 to 3 : 7 to give a dark brown oil (650 mg, 85%). NMR (300 MHz, CDCh): delta 8.52-8.46 (m, 1H), 7.63-7.59 (m, 1H), 7.35 (dd, J = 7.9, 4.5 Hz, 1H), 4.24-4.10 (m, 4H), 2.63 (s, 3H), 1.23 (t, J = 7.0 Hz, 3H); Calculated for CI 1H13N03, 207.09; MS (ESI) (m/z) observed 208.2 (M + 1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium hydroxide; In methanol;Reflux; | General procedure: A suspension of aldehyde intermediate 4 (0.64 mmol) and ketone 5a-5i (0.64 mmol) in methanol (5 mL) was treated with solid sodium hydroxide (0.83 mmol) and refluxed for 3-4 h. After completion of the process, the precipitated solid was filtered off, washed with water and dried under vacuum to give a pure compounds 6a-6i. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 24h; | To a 250 mL RBF was added (S)-1-(4-methoxyphenyl)ethanamine (6.39 g, 42.3 mmol), 1-(3- methylpyridin-2-yl)ethanone (6 g, 44.4 mmol), DCM (Volume: 106 ml) and STAB-H (17.92 g, 85 mmol) at rt and the reaction was stirred for 24h. The reaction was quenched by the addition of 1N NaOH until a pH of 8 was achieved. The phases were separated and the organic layer was treated with 1N NaOH until pH 11 was observed. The DCM layer was dried with MgSO4 filtered and concentrated to an oily residue. The residue was purified via combiflash to separate the diastereomers (~4:1 by crude NMR, 80g column 10-30% gradient over 40 min). 1H NMR (400 MHz, CDCl3): delta= 8.45 (d, J= 4.8 Hz, 1H), 7.34 (d, J= 7.6 Hz, 1H), 7.13 (d, J= 8.5 Hz, 2H), 7.04 (dd, J= 7.8, 4.6 Hz, 1H), 6.82 (d, J= 9.2 Hz, 2H), 3.79 (s, 3H), 3.74 (q, J= 6.0 Hz, 1H), 3.27 (q, J= 5.9 Hz, 1H), 1.24 (d, J= 6.3 Hz, 3H), 1.20 (d, J= 6.3 Hz, 3H); LC/MS 75% MeOH in H2O over 3 minutes, rt = 0.480 at 254 nM, MS (+) 271.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | To a solution of l-(3- methylpyridin-2- yl)ethanone (500 mg, 3.7 mmol) in THF (10 mL) was added methylamine solution (30 wt percent in absolute ethanol, 14.8 mL) and Ti(OEt)4(1.7 g, 7.4 mmol). The reaction mixture was stirred for lOmin at room temperature, before NaB (563 mg, 14.8 mmol) was added, this reaction mixture was stirred for 2h at room temperature. The saturated NaHCC>3 aqueous solution (100 mL) was added and extracted with dichloromethane (100 mL). The organic layer was dried over Na2S04, filtered and evaporated. The residue was purified by silica gel column chromatography (dichloromethane/methanol/ ammonium hydroxide = 100/1/1) to give the desired product (300 mg, 54%) as a yellow oil. H NMR (400 MHz, CDC13) delta 8.44 (d, / = 4.8 Hz, 1H), 7.41 (d, / = 7.2 Hz, 1H), 7.09-7.02 (m, 1H), 3.95 (q, / = 6.4 Hz, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 1.31 (d, / = 6.4 Hz, 3H). |