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CAS No. : | 17288-53-8 |
Formula : | C8H8N2O |
M.W : | 148.16 |
SMILES Code : | COC1=CC2=C(NC=C2)C=N1 |
MDL No. : | MFCD09038907 |
InChI Key : | CCNJNELOBGXDFD-UHFFFAOYSA-N |
Pubchem ID : | 641092 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In DMF (N,N-dimethyl-formamide);Heating / reflux; | [0546] 5-Methoxy-1H-pyrrolo [2,3-c] pyridine-3-carbaldehyde can be prepared from 165 using with 1,3, 5,7-tetraaza-adamantane under refluxing conditions with DMF (D. Mazeas et. al, Heterocycles, 1999,50, 1065-80). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In DMF (N,N-dimethyl-formamide); | [0545] 5-Methoxy-lH-pyrrolo [2,3-c] pyridine 164 can be prepared through cyclization of 6-METHOXY-4-TRIMETHYLSILANYLETHYLNYL-PYRIDIN-3-YLAMINE 163 with cuprous iodide in DMF (D. Mazeas et. al, Heterocycles, 1999,50, 1065-80). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: Preparation of intermediate 164, 5-Methoxy-1H-pyrrolo[2,3-c]pyridine 5-Methoxy-1H-pyrrolo[2,3-c]pyridine 164 can be prepared through cyclization of 6-methoxy-4-trimethylsilanylethylnyl-pyridin-3-ylamine 163 with cuprous iodide in DMF (D. Mazeas et. al, Heterocycles, 1999, 50, 1065-80). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N,N-dimethyl-formamide dimethyl acetal;palladium; In ethanol; ethyl acetate; | A solution of 2-methoxy-4-methyl-5-nitropyridine (4.30 g, 25.57 mmol) and dimethylformamide dimethylacetal (35 ml) was heated at reflux under nitrogen for 40 hours. Ethyl acetate was added to this solution (150 ml), and this mixture was washed with water (150 ml). The aqueous extract was back-extracted with ethyl acetate (100 ml), and the organic extracts were combined, dried (Na2 O4), and evaporated under reduced pressure to yield a purple solid. The solid was dissolved in absolute ethanol (200 ml), and 5% palladium on carbon (3.0 g) was added to this solution which was shaken under a hydrogen atmosphere (3 atm) for 3 hours. The resultant reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. Flash chromatography of the residue yielded compound 9 (2.05 g, 13.84 mmol, 54% last step, 50% overall) as a white crystalline solid: mp, 123-124 C.; IR (KBr) 1625, 1580, 1490, 1460, 1320, 1150 cm-1; 1 H NMR (DMSO-d6) delta 11.28 (br s, 1H), 8.37 (s, 1H), 7.57 (t, J=2.8 Hz, 1H), 6.86 (s, 1H), 6.33 (br m, 1H), 3.82 (s, 3H); 13 C NMR (DMSO-d6) delta 157.2, 136.4, 131.5, 130.7, 130.0, 99.6, 96.8, 53.4; LRMS (m/z, relative intensity) 149 (20), 148 (M+, 98), 147 (100), 119 (46), 118 (79), 117 (26), 105 (31), 91 (15), 70 (16); HRMS calculated for C8 H8 N2 O:148.0657, found: 148.0613. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With thionyl chloride; In N-methyl-acetamide; dichloromethane; toluene; | EXAMPLE 12 5-Methoxypyrrolo[2,3-c]pyridine (Compound 9) A mixture of 4-methyl-5-nitro-1H-pyridine-2-one (5.00 g, 32.44 mmol), thionyl chloride (20 ml), and two drops of dimethylformamide was heated atreflux under nitrogen for 52 hours. The resultant orange colored solution was evaporated under reduced pressure, and a small amount of anhydrous toluene was added and then removed via evaporation under reduced pressure to remove traces of thionyl chloride. The residual oil then passed througha silica gel filter (dried at 150 C. under vacuum overnight, approximately 100 g) followed by methylene chloride (1 1). This filtrate was evaporated under reduced pressure to afford 2-chloro-4-methyl-5-nitropyridine (5.30 g, 30.71 mmol, 95%) as an orange oil, which crystallized below 0 C.; IR (CHCl3) 1605, 1550, 1520, 1450, 1360, 1345 cm-1; 1 H NMR (CDCl3) delta 9.03 (s, 1H), 7.83 (s, 1H), 2.60 (s, 3H); LRMS (m/z, relative intensity) 174 (25), 173 (19), 172 (M+, 68), 157 (74), 155 (100), 128 (27), 101 (47), 100(55], 99 (74), 90 (43), 75 (36). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;copper acetylacetonate; In dimethyl sulfoxide; at 130℃; for 10h; | To a mixture of <strong>[17288-53-8]5-methoxy-1H-pyrrolo[2,3-c]pyridine</strong> (6.00 g, 40.5 mmol; cf. D.Mazeas et al., Heterocycles 50 (1999), 1065), copper(ll) acetylacetonate (1.06 g, 4.05 mmol) and potassium carbonate (11.2 g, 81.0 mmol) in DMSO (63 ml) was added iodobenzene (4.99 ml, 44.6 mmol). The reaction mixture was stirred at 130 0C for 10 h. The mixture was then cooled to room temperature, and a solution of ammonium chloride (20 % in water) was added. The mixture was filtered through celite and the filtrate extracted three times with EA. The organic layers were combined, dried over sodium sulfate, filtered and evaporated under reduced pressure. <n="90"/>Column chromatography of the residue on silica gel (EA/HEP) gave 8.43 g of the title compound.LC/MS (method LC4): m/z = 225 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Zinc (15.97 g, 244.0 mmol) was suspended in acetic acid (240 ml) and cooled to 0C. Solid 2-(2-chloro-5-nitropyridin-4-yl)-N,N-dimethylethenamine (5.56 g, 24.42 mmol) was added portion- wise over about 5 minutes and then the reaction mixture was placed under an atmosphere of argon. The reaction was stirred for 18 h, after which time LCMS analysis indicated that the reaction was complete. The mixture was filtered through Celite, washing with EtOAc. The filtrate was concentrated to give a brown oil. The reaction mixture was partitioned between EtOAc and IN NaOH. The aqueous layer was extracted with EtOAc (3x) and the combined organic layer was dried over Na2S04, filtered and concentrated. The residue was adsorbed onto silica gel and purified by flash column chromatography on silica gel, eluting with EtOAc/isohexane (0-100%) to give 2.79 g of an off-white solid, that is approximately a 10: 1 mixture of the title compound along with 5-methoxy-lH-pyrrolo[2,3-c]pyridine as a minor impurity. The mixture was taken forward into the next step as is. LRMS (ESI) calc'd for (C7H5C1N2) [M+H]+, 153; found 153 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 130℃; | 1. The mixture of 2-methoxy-4-methyl-5-nitropyridine (1.68g, 10.0 mmol) and 1,1- dimethoxy-N,N-dimethylmethanamine (14 Ml, 103 mmol) in 10 mL of DMF was heated at 130C overnight, cooled to RT, diluted with EtOAc, washed with water and brine, dried (MgS04), and concentrated. The residue was dissolved in 70 mL of EtOH. To this solution was added 1.06 g of 10% Pd/C. The mixture was stirred under 1 atm of hydrogen atmosphere over 4 days, filtered through a pad of Celite, and washed with EtOH. The filtrate was concentrated to give crude 5-methoxy-lH-pyrrolo[2,3-c]pyridine (quant). H NMR (399 MHz, DMSO-d6) delta ppm 11.26 (1 H, br. s.), 8.33 (1 H, s), 7.53 (1 H, d, 7=2.7 Hz), 6.73 - 6.88 (1 H, m), 6.32 (1 H, d, 7=3.1 Hz), 3.30 (3 H, s). |