Structure of 1152749-21-7
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CAS No. : | 1152749-21-7 |
Formula : | C8H11N3O2 |
M.W : | 181.19 |
SMILES Code : | O=C(N1CCOCC1)C2=CNN=C2 |
MDL No. : | MFCD12142788 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 |
* 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 benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃; | (1) Preparation of 4-(1H-pyrazol-4-ylcarbonyl)morpholine A suspension of <strong>[37718-11-9]1H-<strong>[37718-11-9]pyrazole-4-carboxylic acid</strong></strong> (1.05 g), 1-{3-(dimethylamino)propyl}-3-ethylcarbodiimide hydrochloride (2.5 g), 1-hydroxybenzotriazole hydrate (1.6 g) and morpholine (1.2 g) in chloroform (18 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (eluding solvent: chloroform:methanol = 100:0 to 95:5) and silica gel column chromatography (eluding solvent: chloroform:methanol = 100:0 to 90:10). The resulting colorless solid was washed with ethyl acetate to give the titled compound (1.00 g) as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; at 120℃; for 1.5h; | (2) Preparation of 4-[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl]carbonyl}morpholine A suspension of (2R)-1-[3-(4-iodophenoxy)propyl]-2-methylpyrrolidine obtained in Example 1-(2) (0.30 g), <strong>[1152749-21-7]4-(1H-pyrazol-4-ylcarbonyl)morpholine</strong> obtained in Example 6-(1) (0.19 g), (rac-trans-N,N'-dimethylcyclohexane-1,2-diamine, (0.049 g), copper iodide (0.017 g) and cesium carbonate (0.57 g) in N,N-dimethylformamide (0.5 mL) was stirred at 120C for 1.5 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by NH-type silica gel column chromatography (eluding solvent: n-hexane:ethyl acetate = 2:1 to 1:1). The resulting crystal was washed with isopropyl ether to give the titled compound (0.20 g) as a white solid. 1H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.08 (d, J=6.0 Hz, 3 H), 1.37-1.46 (m, 1 H), 1.64-1.82 (m, 2 H), 1.87-2.05 (m, 3 H), 2.11 (q, J=8.7 Hz, 1 H), 2.16-2.23 (m, 1 H), 2.25-2.33 (m, 1 H), 2.94-3.02 (m, 1 H), 3.13-3.20 (m, 1 H), 3.67-3.81 (m, 8 H), 4.01-4.10 (m, 2 H), 6.94-7.01 (m, 2 H), 7.52-7.58 (m, 2 H), 7.78 (s, 1 H), 8.13 (s 1 H) MS (ESI/APCI Dual) (Positive) m/z; 399(M+H)+ | |
2.28 g | With copper(l) iodide; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; In N,N-dimethyl-formamide; | (1) According to the method described in WO2009 / 063953,(2R) -1- [3- (4-Iodophenoxy) propyl] -2-methylpyrrolidine (Compound [15]) (3.50 g),Compound [5] (2.20 g), rac-trans-N, N′-dimethylcyclohexane-1,2-diamine (0.575 g),Copper (I) iodide (0.192 g),And cesium carbonate (6.58 g) were reacted in N, N-dimethylformamide (6.0 mL) to obtain compound [1].(2) To the compound [1] obtained in (1) above,Isopropyl ether was added for crystallization.The obtained crystals are filtered and dried,The title crystal (2.28 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With caesium carbonate;copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; In N,N-dimethyl-formamide; at 130℃; for 6.0h; | (3) Preparation of [1-(3-fluoro-4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl](morpholin-4-yl)methanone To a solution of (2R)-1-[3-(4-bromo-2-fluorophenoxy)propyl]-2-methylpyrrolidine obtained in Example 62-(2) (0.72 g) and morpholin-4-yl(1H-pyrazol-4-yl)methanone (0.45 g) in N,N-dimethylformamide (3 mL), cesium carbonate (1.6 g), copper iodide (0.1 g) and (1R,2R)-N,N'-dimethylcyclohexane-1,2-diamine (0.36 mL) were added and the mixture was heated to 130C, at which it was stirred for 6 hours. The reaction mixture was cooled to room temperature and filtered to remove insoluble materials, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluding solvent: chloroform:methanol = 11:1 to 3:1) and NH-type silica gel column chromatography (eluding solvent: chloroform:methanol = 10:0 to 100:1) to give the titled compound (0.34 g, 36%) as a colorless solid. 1H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.09 (d, J=6.0 Hz, 3 H), 1.37-1.47 (m, 1 H), 1.66-1.74 (m, 1 H), 1.74-1.83 (m, 1 H), 1.87-1.96 (m, 1 H), 1.99-2.08 (m, 2 H), 2.08-2.16 (m, 1 H), 2.18-2.27 (m, 1 H), 2.27-2.35 (m, 1 H), 2.96-3.05 (m, 1 H), 3.13-3.21 (m, 1 H), 3.70-3.81 (m, 8 H), 4.10-4.21 (m, 2 H), 7.02-7.09 (m, 1 H), 7.32-7.37 (m, 1 H), 7.45-7.51 (m, 1 H), 7.76-7.81 (m, 1 H), 8.14 (s, 1 H) MS (ESI/APCI Dual) (Positive) m/z; 417(M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 60℃; | A 40-mL vial was charged with c/'s-5-(methyl(4- (trifluoromethyl)benzyl)amino)hexahydrocyclopenta[c]pyrrole-2(lH)-carbonyl chloride (361 mg, 1.00 mmol, 1.00 equiv), THF (10 mL), mo holino(lH-pyrazol-4-yl)methanone (181 mg, 1.00 mmol, 1.00 equiv), N,N-diisopropylethylamine (258 mg, 2.00 mmol, 2.00 equiv) and 4- dimethylaminopyridine (12.2 mg, 0.100 mmol, 0.10 equiv). The resulting solution was stirred overnight at 60 C and quenched by water (15 ml). The mixture was extracted with EtOAc (3 x 10 ml) and the organic layers were combined, washed with water (3 x 10 ml), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC. Purification resulted in 66.7 mg (13% yield) of (c/5-5- (methyl(4-(trifluoromethyl)benzyl)amino)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)(4- (mo holine-4-carbonyl)-lH-pyrazol-l-yl)methanone as a light yellow oil. 1H NMR (400 MHz, Chloroform- δ 8.42 (s, 1H), 7.83 - 7.84 (m, 2H), 7.60 (d, J= 7.8 Hz, 1H), 7.52 (t, J= 7.6 Hz, 1H), 7.32 (t, J= 7.6 Hz, 1H), 3.67 - 4.13 (m, 14H), 2.92 - 3.01 (m, 1H), 2.72 (br, 2H), 2.05 - 2.17 (m, 5H), 1.52 (br, 2H). LCMS (ESI, m/z): 506[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With triethylamine; In tetrahydrofuran; at 20℃; for 0.2h; | A 250-mL round-bottom flask was charged with morpholine (6.70 g, 76.9 mmol, 1.00 equiv), triethylamine (15.6 g, 154 mmol, 2.00 equiv), THF (100 mL) and lH-pyrazole-4- carbonyl chloride (10.0 g, 76.6 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at room temperature and concentrated under reduced pressure. The residue was chromatographed on a silica gel column to provide 9.80 g (71% yield) of morpholino(lH-pyrazol-4-yl)methanone as a white solid. LCMS (ESI, m/z): 182 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
148 g | With 1,8-diazabicyclo[5.4.0]undec-7-ene; at 115 - 123℃; for 14.0h; | Compound [6 '] (140 g) to morpholine [7] (174 g),Add DBU (30.4g)The mixture was stirred at 115 C to 123 C for 14 hours.Meanwhile, distillate (15.1 g) was withdrawn.The reaction mixture is cooled to 78 C.Crystallization with toluene gave the title compound as pale yellow crystals [5](148 g) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
218 g | With potassium carbonate; copper(l) chloride; N,N`-dimethylethylenediamine; In 1-methyl-pyrrolidin-2-one; water; at 125 - 130℃; for 8.5h; | Potassium carbonate was added to the compound [5] (127 g) obtained in Example 1.(97.0 g), copper (I) chloride (6.33 g),NMP (550 g), DMEDA (22.5 g) are added,Furthermore, compound [4 '] obtained in Example 2 (195 g)And washed with NMP (20.1 g).Add water (5.71 g) to the mixture.The mixture was stirred at 125 to 130 C. for about 8 hours and 30 minutes. The reaction mixture was allowed to cool to room temperature and toluene (1520 g)And 28% aqueous ammonia (895 g) were added for liquid separation.28% aqueous ammonia (380 g) was added to the organic layer and the layers were separated.The organic layer was washed with water and concentrated under reduced pressure,Crystallization of the title compound [1] as white crystals by crystallization with tert-butyl methyl ether (MTBE)(218 g) was obtained. |
A418820 [1153845-34-1]
N,N-Diethyl-1H-pyrazole-4-carboxamide
Similarity: 0.83
A418820 [1153845-34-1]
N,N-Diethyl-1H-pyrazole-4-carboxamide
Similarity: 0.83