Structure of 1006-64-0
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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. : | 1006-64-0 |
| Formula : | C10H13N |
| M.W : | 147.22 |
| SMILES Code : | C1CNC(C1)C1=CC=CC=C1 |
| MDL No. : | MFCD01631835 |
| InChI Key : | JUTDHSGANMHVIC-UHFFFAOYSA-N |
| Pubchem ID : | 261892 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H332-H335 |
| Precautionary Statements: | P261-P280-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.


[ 1006-64-0 ]
[ 796600-15-2 ]
[ 1006-64-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 37% | With 4-methyl-morpholine; at 150℃; | Heat <strong>[796600-15-2]2-chloro-4-fluoro-3-methyl-benzonitrile</strong> (144 mg, 0.85 mmol) and 2- . phenyl-pyrrolidine (0.15 g, 1.02 mmol, 1.20 equivalents) in N-methylmorpholine (0.11 ml, 1.02 mmol, 1.20 equivalents) at 150 0C overnight. Allow the reaction mixture to cool to room temperature, dilute with dichloromethane (1 ml), load on silica, and purify by chromatography (12 g silica gel, 0 to 100% ethyl acetate/hexanes over 20 minutes) to obtain 150 mg of an oily residue. Recrystallize from ethyl acetate/hexanes to obtain the title compound (92 mg, 37%). LCMS(APCI+): 297.0 (M+l)+; 1H NMR (400 MHz, CDCl3): delta 7.25 (s, 2H), 7.19 (m, 2H), EPO <DP n="58"/>6.65 (d, IH), 4.70 (m, IH), 4.06 (m, IH), 3.18 (m, IH), 2.44 (m, IH), 2.43 (s, 3H), 2.12 (m, IH), 1.94 (m, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87% | With lithium aluminium tetrahydride; In tetrahydrofuran; at -5 - 20℃; for 2h; | (4) (S)-5-phenylpyrrolidin-2-one (40 g, 0.25 mol) was dissolved in tetrahydrofuran (800 mL), cooling to -5-5 deg. C, lithium aluminum hydride (23.6 g, 0.62 mol) was added in portions to keep the internal temperature below 10 C, and the mixture was stirred at room temperature for 2 h. Quenched with water (23.6 g), keeping the temperature within -5-5 deg. C, followed by stirring at room temperature for 1 h, filtered, and concentrated to give 32 g of a colorless oil, in 87% yield. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With triethylamine; In acetonitrile; at 50℃;Inert atmosphere; | General procedure: Intermediate 3 (24 g, 30.08 mmole) was dissolved in anhydrous MeCN (1200 mL), followed by addition of R(+)-3-(4,4-dimethylpyrrolidin-2-yl) pyridine (+)-phencyphos salt (15.11 g. 36.10 mmol, 1.2 eq) and TEA (10.5 mL, 75.20 mmol, 2.5 eq) in a 2-L round bottom flask. The mixture was heated to 50 deg C overnight. The reaction mixture was then concentrated to dryness and dissolved in MeOH (1200 mL) and TEA (4 mL, 1eq) and stirred to 50 deg C overnight to remove the acetyl group. The mixture was then concentrated to dryness, dissolved in DCM (300 mL) and aq saturated bicarbonate (300mL) and extracted with DCM (4 x 300 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to dryness to afford 25g of crude product. Silica gel chromatography (0-7% MeOH/DCM) yielded final product 4f (12.5 g, 50%) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | In acetonitrile; at 20℃; for 8h; | General procedure: To the corresponding amine 9 (0.710mmol) in acetonitrile (5mL), 3-phenylpropyl isocyanate 10 (0.645mmol) was added and allowed to stir for 8hat ambient temperature. The resulting mixture was portioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude mixture was subjected to column chromatography to obtain the pure compounds. 5.1.1.16 (S)-2-phenyl-N-(3-phenylpropyl)pyrrolidine-1-carboxamide (8i(S)) Yield 82%; Yellow oil; IR (neat): 3335, 3025, 2864, 1628, 1527, 1494, 1346 cm-1; 1H NMR (CDCl3) delta 1.60-1.67 (m, 2H), 1.82-194 (m, 3H), 2.35-2.42 (m, 3H), 3.04-3.11 (m, 1H), 3.15-3.22 (m, 1H), 3.63-3.72 (m, 2H), 4.01 (bs, 1H), 4.64-4.67 (m, 1H), 7.01 (d, J = 7.60 Hz, 2H), 7.13-7.37 (m, 8H); 13C NMR (CDCl3) delta 23.02, 31.58, 32.84, 36.78, 39.87, 47.27, 60.84, 125.74, 125.78, 127.57, 128.33, 128.34, 128.97, 141.76, 143.33, 157.12; HRMS Calcd for C20H24N2O m/z [M+H] 309.1967, found 309.1996. |

[ 1006-64-0 ]
[ 76-05-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 41% | General procedure: To a mixture of 3-chloro-N-(2,4-dimethoxybenzyl)-4-formyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.30 g, 0.66 mmol), (S)-2-methylpyrrolidine 4-methylbenzenesulfonic acid salt (0.34 g, 1.32 mmol), and potassium acetate (0.13 g, 1.32 mmol) in 1,2-dichloroethane (10 mL) was added sodium triacetoxyborohydride (0.28 g, 1.32 mmol). The resulting mixture was stirred for 24 h and then diluted with EtOAc (50 mL). The mixture was washed with saturated aqueous ammonium chloride (50 mL), brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in DCM (20 mL) and TFA (5 mL) was added. The mixture was stirred for 40 minutes, concentrated in vacuo, quenched with MeOH (10 mL), filtered, and concentrated in vacuo. The residue was purified by reverse-phase HPLC (Gemini NX, C-18, 5 him, 30 x 150 mm; mobile phase: A water (0.1% TFA), B CH3CN (0.1% TFA); gradient:15% B (2 mm), followed by 15-55% B (8 mm); flow rate: 60 mL/min) to provide the titlecompound as a trifluoroacetate salt as a colorless solid (0.11 g, 34% yield); Following the procedure as described for Example 45, step 3 and making non-critical variations as required to replace (S)-2-methylpyrrolidine 4-methylbenzenesulfonic acid salt with<strong>[1006-64-0](S)-<strong>[1006-64-0]2-phenylpyrrolidine</strong></strong>, the title compound was obtained as a trifluoroacetate salt as a colorless solid (0.10 g, 41% yield). MS (ES+) m/z: 435.1, 437.0 (M + 1). ?H NMR (300 MHz, MeOD-d4) 5 8.20 (s, 1H), 7.85-7.84 (m, 1H), 7.79 (dd,Jr= 1.8, 8.0 Hz, 1H), 7.63 (d,J= 8.0 Hz, 1H), 7.52-7.48 (m, 2H), 7.46-7.41 (m, 3H), 4.63-4.57 (m, 1H), 4.49 (d, J 13.4 Hz, 1H), 4.37 (d, J- 13.4 Hz, 1H), 3.70-3.62 (m, 1H), 3.57-3.48 (m, 1H), 2.63-2.52 (m, 1H), 2.38-2.17 (m, 3H) (Note: Exchangeableprotons not observed). |

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