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CAS No. : | 49608-01-7 | MDL No. : | MFCD00082739 |
Formula : | C8H8ClNO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | ILDJJTQWIZLGPO-UHFFFAOYSA-N |
M.W : | 185.61 | Pubchem ID : | 2799611 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
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* 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 |
---|---|---|
59% | With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 16h; | To a solution of 19-2B (500 mg, 2.693 mmol) in MeOH (5 mL) was added sodium borohydride (153 mg, 4.04 mmol) portion wise at 0 C and stirred at RT for 16 hr. The reaction was quenched with saturated ammonium chloride and diluted with EtOAc (50 mL) washed with water (50 mL), brine (20 mL) and dried over Na2S04, and the organic phase was concentrated under reduced pressure to get crude compound. Obtained crude was purified using silica gel chromatography (30% EtOAc in hexanes) to afford 19-3B (230 mg, 1.60 mmol, 59% yield) as a pale yellow solid. MS (ESI): m/z 144.0 (M+l)+. |
58% | With sodium tetrahydroborate; In ethanol; at 20℃; for 41h; | To a solution of ethyl 6-chloronicotinate (25.8 g, 0.139 mol) in ethanol was added sodium borohydride (10.5 g, 0.278 mol), followed by stirring under an atmosphere of nitrogen gas at room temperature. After 41 hours, the reaction mixture was concentrated and then the residue was diluted with a saturated aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography (elution solvent; hexane, hexane:ethyl acetate=4:1, 2:1, and 3:2), to give the title compound (11.7 g, 58%) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm; 4.54 (2H, d, J=5.6Hz), 5.43 (1H, t, J = 5.6 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.80 (1H, dd, J = 2.4, 8.4 Hz), 8.35 (1H, d, J = 2.4 Hz). |
With lithium aluminium tetrahydride; In tetrahydrofuran; toluene; at -78 - 0℃; for 1h; | EXAMPLE 2; Synthesis of N2- [ (lS)-I- (4-15- [l- (aminocarbonyl) cyclopropyl] pyridin-2-yl} phenyl)-2, 2,2-trifluoroethyl]- Nl- (1-cyanocyclopropyl)-4-fluoro-L-leucinamide; Step 1 : Preparation of (6-chloropyridin-3-yl) methanol; To a-78 C solution of ethyl 6-chloronicotinate (10 g) in 250 mL of THF was slowly added 126 mL of lithium aluminium hydride (1.5 M in toluene). The mixture was stirred at 0 C for 1 hour. Poured into saturated aqueous tartaric acid (200 mL) and extracted with ethyl acetate (2 X 200 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on Si02 using ethyl acetate and hexanes (1: 2 to 1: 1) to yield the title compound. 'H NMR (CD3COCD3) 8 8.35 (1H, s), 7.80 (1H, d), 7.40 (1H, d), 4. 68 (2H, d), 4.55 (1H, t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; at 60℃; | Step 1: Ethyl 6-{4-[(1-[(1, 1-DIMETHYLETHYL) oxy] CARBONYL}-4-PIPERIDINYL) OXY]-1- PIPERIDINYL}-3-PYRIDINECARBOXYLATE tert-Butyl 4- (4-piperidinyloxy)-1-piperidinecarboxylate (D4) (1. 7G), potassium carbonate (1.5g) and ethyl 6-chloro-3-pyridinecarboxylate (1.0 G) were heated at 60C under argon overnight. The reaction mixture was evaporated and redissolved in DCM (100 ML) and washed with saturated sodium hydrogen carbonate (3 x 50ml), dried (MgSO4) and evaporated to give a crude product which was chromatographed [silica gel, eluting with (10% NH3 in MeOH/DCM, 0-10%] to give the subtitle compound (1.43 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of <strong>[1196473-37-6]3H-benzo[c][1,2]oxaborole-1,6-diol</strong> (1.2 g, 8.0 mmol) in anhydrous dioxane (100 mL) was slowly added KHMDS (48 mL, 0.5 M solution in toluene, 24.0 mmol) at 0° C. After stirring for 15 min at room temperature, 6-chloro-nicotinic acid ethyl ester (2.97 g, 16.0 mmol) was added slowly to the reaction mixture at 0° C. The resulting mixture was stirred at 80° C. for 22 h. The reaction quenched by adding cold brine at 0° C. and the mixture was acidified to pH 3 using diluted hydrochloric acid. The resulting mixture was extract with EtOAc. The extract was washed with brine, dried and concentrated to dryness. The residue was purified by chromatography on silica gel (DCM/methanol=40:1) to give 0.521 g of material. This material was purified by prep-TLC (silica gel, THF/hexanes/AcOH=2:4:trace) to give 0.261 g of purer material which was purified again by chromatography on silica gel (DCM/methanol=40:1) to give 0.109 g of pure product as a pale-yellow solid. Mp 84-85° C. 1H NMR (400 MHz, DMSO-d6) delta 9.23 (s, 1H), 8.68 (d, J=2.34 Hz, 1H), 8.31 (dd, J=8.50, 2.34 Hz, 1H), 7.41-7.54 (m, 2H), 7.30 (dd, J=8.20, 2.34 Hz, 1H), 7.15 (d, J=8.50 Hz, 1H), 5.02 (s, 2H), 4.32 (q, J=7.03 Hz, 2H), 1.31 (t, J=7.03 Hz, 3H). MS (ESI) m/z=300 [M+H]+. |
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