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CAS No. : | 25808-30-4 | MDL No. : | MFCD00012587 |
Formula : | C3H7ClN2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DFKBQHBEROHUNF-UHFFFAOYSA-N |
M.W : | 106.55 | Pubchem ID : | 117641 |
Synonyms : |
|
Num. heavy atoms : | 6 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.67 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 26.05 |
TPSA : | 35.82 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.68 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 0.38 |
Log Po/w (WLOGP) : | 0.53 |
Log Po/w (MLOGP) : | -0.33 |
Log Po/w (SILICOS-IT) : | -0.42 |
Consensus Log Po/w : | 0.03 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.67 |
Solubility : | 22.6 mg/ml ; 0.212 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.7 |
Solubility : | 21.4 mg/ml ; 0.201 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.67 |
Solubility : | 23.0 mg/ml ; 0.216 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.21 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
70% | at 90℃; | bl . l) Compound (2) To a solution of cyano-N-methylmethanaminium chloride (6.4 g, 39.9 mmol) in chlorobenzene (50 ml) was added dropwise oxalyl chloride (12 ml, 137 mmol) at r. t., then the resulting solution was heated slowly to 90 °C and stirred overnight. The solvent was removed, the residue was purified by column chromatography on silica gel (PE:EA=10: 1) to give the title compound as yellow oil (5 g, 70percent yield). LC-MS (ESI+): m/e 178 (M+H)+, Rt: 1.54 min. |
60% | at 80℃; for 8 h; | d) 3,5-Dichloro-1-methyl-1H-pyrazin-2-one (4c)[0245][0246]3.29 g (30.8 mmoles) of methylamino-acetonitrile hydrochloride is placed in the presence of 19.6 g (154 mmoles) of oxalyl chloride in 30 ml of 1,2-dichlorobenzene. The mixture is heated for 8 hours at 80° C. After concentrating the reaction medium to dryness, the residue obtained is purified by flash chromatography (Petroleum ether-CH2Cl2 gradient 100-0 to 0-100). 3.35 g of intermediate 4c is obtained in beige powder form (yield: 60percent).[0247]TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH: 90-10, Rf=0.79. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | at 0 - 55℃; for 16 h; | To a suspension of methylamino acetonitrile hydrochloride (20 g, 142.0 mmol) in DCM (1300 ml), was added oxalyl bromide (54 ml, 188.67 mmol) followed by slow addition of DMF (1.5 ml) at 0°C. The reaction mixture was stirred at 55°C for 16 h. DCM was concentrated under reduced pressure, the residue obtained was purified by column chromatography by eluting with 2percent MeOH/CH2Cl2 to afford the desired compound as a pale yellow solid (34 g, 92 percent); *H NMR (400MHz, DMSO-dg) δ 8.1 (s, 1H), 3.4 (s, 3H). LC-MS: 268.9 (M+l)+. |
92% | at 0 - 55℃; for 16 h; | To a suspension of methylamino acetonitrile hydrochloride (20 g, 142.0 mmol) in DCM (1300 mL), was added oxalyl bromide (54 mL, 188.67 mmol) followed by slow addition of DMF (1.5 mL) at 0°C. The reaction mixture was stirred at 55°C for 16 h. DCM was concentrated underreduced pressure, the residue obtained was purified by colunm chromatography by eluting with2percent MeOH/CH2C12 to afford the desired compound as a pale yellow solid (34 g, 92percent); 1H NMR(400 MHz, DMSO-d6) ö 8.1 (s, 1H), 3.4 (s, 3H). LC-MS: 268.9 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: for 18 h; Reflux Stage #2: for 18 h; Reflux |
A 5-L three-neck RBF equipped with a mechanical stirrer, thermoregulator, reflux condenser andnitrogen inlet was charged with compound 5(181.0 g, 1.66 mol) and anhydrous DCM (1.5 L). Oxalyl bromide (367 g, 1.70 mol) wasadded and the stirring suspension was heated to reflux for 18 h (Caution: poisonous gas evolution). The reaction mixture was then cooled to 0 °C in an ice/water bath before anhydrous DMF (186 g, 2.55 mol) was slowly added (Caution: reaction was exothermic andfoaming with poisonous gas evolution). Dueto the exothermic nature of the reaction, mixture temperature rose to 12°C. Additional oxalyl bromide (550 g,2.55 mol) was added portion-wise (Caution: reaction was exothermic withpoisonous gas evolution). The mixturetemperature rose further to 16 °C. Afterthe addition, the reaction mixture was stirred in a cooling bath for 20 min andat 25 °C for 30 min and was heated to reflux for 18 h. Upon cooling to 25 °C, the reaction mixturewas poured into a 2.5 gal. carboy containing saturated aqueous sodiumbicarbonate (2 L) (Caution:foaming). Sodium bicarbonate (~405 g)was added portion-wise to adjust thepH to 8 (Caution: foaming). After separation, the aqueous layer wasextracted with DCM (3 × 1 L). Thecombined organic layers were dried over sodium sulfate, filtered andconcentrated under vacuum. The resultingresidue suspended in DCM (approximately 250 mL) was purified on a silica gelplug (glass frit, 6” diameter, 2.5” height of silica) and eluted with methylenechloride (approximately 5 L total). After evaporation, the desired product VI (317.2 g, 71percent) was obtained as a light reddish-brown solid (mp: 94–95 C); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine In dichloromethane at 20℃; for 168 h; | To a suspension of methylaminoacetonitrile hydrochloride (11.45 g, 107.4 mmol) in DCM (100 ml_) was added triethylamine (31.5 mL, 226 mmol), followed by di-tert-butyl dicarbonate (22.3 g, 102.2 mmol) and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was filtered, concentrated in vacuo and purified over silica using a gradient of 10-20percent ethyl acetate/cyclohexane. The pure fractions were combined and concentrated to afford the title compound (11.94 g, 69percent) as a colourless liquid. LC-MS (Method 5): 2.82 min, [M+H]+ 171.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In a vessel load: 120 g of nitrobenzene and 53.3 g of aluminium chloride making attention to the exothermic effect, then 21.2 g of methylaminoacetonitrile hydrochloride were added. Then 27.6 g of veratrole were poured into the mixture. In a few minutes a homogeneous solution was obtained, then hydrochloric acid was bubbled through the solution vigorously for 6 hrs, at a temperature of 25° C.The mixture was then poured into 320 ml of water under cooling. Then the organic layer was separated at 75° C. and the aqueous layer undergoes to vacuum distillation (50 ml are distilled off) in order to remove the latest traces of solvent. The obtained aqueous layer was then treated with 4.9 g of decolorizing charcoal for 1 hr at 80° C. Then the charcoal was filtered off and the panel washed with 50 ml of water which were joined together with the mother liqueur. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; In dichloromethane; at 20℃; for 168h; | To a suspension of methylaminoacetonitrile hydrochloride (11.45 g, 107.4 mmol) in DCM (100 ml_) was added triethylamine (31.5 mL, 226 mmol), followed by di-tert-butyl dicarbonate (22.3 g, 102.2 mmol) and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was filtered, concentrated in vacuo and purified over silica using a gradient of 10-20percent ethyl acetate/cyclohexane. The pure fractions were combined and concentrated to afford the title compound (11.94 g, 69percent) as a colourless liquid. LC-MS (Method 5): 2.82 min, [M+H]+ 171.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; N-methyl-acetamide; ethyl acetate; | Step 1: (2-Amino-ethyl)-methyl-carbamic acid tert-butyl ester To a cooled solution of methyl aminoacetonitrile hydrochloride (5.4 g, 50 mmol) in tetrahydrofuran:dimethylformamide (15 mL each) was added over 30 minutes, a solution of di-t-butyl dicarbonate (9.0 g, 50 mmol) and triethylamine (3.4 mL, 24 mmol) in tetrahydrofuran (30 mL). The reaction was stirred overnight at room temperature. The solution was concentrated and the residue taken up in ethyl acetate. The organic solution was washed with brine, dried over MgSO4, filtered and concentrated to give a brownish oil; 8.38 g, (98percent yield). MS-APCI: M+1=171. It was used without further purification. The above product was reduced in the presence of Raney nickel, in ethanol/triethylamine. The catalyst was removed and washed with ethanol. The filtrate was concentrated to give the desired product as a brownish oil; 7.13 g (84percent yield). MS-ACPI: M+1=175. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
List B-Amines:1. dimethylamine...9. dibenzylamine10. methyl-phenyl-amine11. allyl-methyl-amine12. methyl-prop-2-ynyl-amine13. methylamino-acetonitrile hydrochloride14. 1-(4-fluoro-phenyl)-piperazine15. furan-2-ylmethyl-methyl-amine16. piperidine-3-carboxylic acid amide... | ||
1. dimethylamine...9. dibenzylamine10. methyl-phenyl-amine11. allyl-methyl-amine12. methyl-prop-2-ynyl-amine13. methylamino-acetonitrile hydrochloride14.1-(4-fluoro-phenyl)-piperazine15. furan-2-ylmethyl-methyl-amine16. piperidine-3-carboxylic acid amide... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In ethanol; | j) from (E)-[4-(4-bromo-but-2-enyloxy)-phenyl]-(4-bromo-phenyl)-methanone and methylaminoacetonitrile.hydrochloride with triethylamine in ethanol there is obtained (E)-[[4-[4-(4-bromo-benzoyl)-phenoxy]-but-2-enyl]-methyl-amino]-acetonitrile which is converted into the hydrochloride, MS: m/e 399 (M+H+, 1Br), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; N,N-dimethyl-formamide; | WORKING EXAMPLE 64 (Production of Compound 64) In DMF (3 ml) was dissolved (E)-N-[4-(chloromethyl)phenyl]-3- (4-methylphenyl)cinnamamide (200 mg), and to the solution were added methylaminoacetonitrile hydrochloride (77 mg) and potassium carbonate (382 mg). The mixture was stirred at room temperature for 14 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetatediisopropylether to give (E)-N-[4-[N-(cyanomethyl)-N-methylaminomethyl]phenyl]-3-(4-methylphenyl)cinnamamide (Compound 64) (129 mg) as colorless crystals. mp 163-165° C.; Elemental Analysis for C26 H25 N3 O.0.1H2 O; Calcd: C, 78.60; H, 6.39; N, 10.58. Found: C, 78.44; H, 6.32; N, 10.35. IR (KBr) cm-1: 3250, 3055, 1662, 1626, 1599, 1535, 1516, 1412, 1344, 1184, 982, 822, 791; 1 H NMR (200 MHz, CDCl3) delta: 2.42 (3H, s), 2.44 (3H, s), 3.46 (2H, s), 3.59 (2H, s), 6.61 (1H, d, J=15.4 Hz), 7.23-7.65 (12H, m), 7.74 (1H, s), 7.83 (1H, d, J=15.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; ethyl acetate; N,N-dimethyl-formamide; | Step 1 4,5-Dimethyl-2-(2-methylbenzoyl)benzoic acid N-cyanomethyl-N-methylamide A mixture of 4,5-dimethyl-2-(2methylbenzoyl)benzoic acid (7.7 g), dichloromethane(100ml), oxalyl chloride(2.74 ml) and N,N-dimethylformamide (3 drops) was stirred at room temperature for 2 hours. The solvent was evaporated, and the residue was dissolved in dichloromethane(50 ml). The solution was added dropwise to a mixture of <strong>[25808-30-4]N-methylaminoacetonitrile hydrochloride</strong>(4.86 g), triethylamine(12.0 ml), and dichloromethane(70 ml) with stirring and ice-cooling. The mixture was stirred at room temperature for 12 hours. The solvent was evaporated, and to the residue was added ethyl acetate. The mixture was washed successively with water, dil.HCl, aq.NaHCO3, and water, and dried(MgSO4). The solvent was evaporated to provide the title compound as a colorless oil (9.2 g). NMR (200 MHz, CDCl3)ppm: 2.26 (3H, s), 2.35 (3H, s), 2.37 (3H, s), 2.99 (3H, s), 4.47 (2H, s), 7.05-7.40 (6H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; ethyl acetate; N,N-dimethyl-formamide; | Reference Example 38 2,6,7-Trimethyl-4-(2-methylphenyl)-1(2H)-isoquinolinone-3-carboxylic acid Process 1 A mixture of 4,5-dimethyl-2-(2-methylbenzoyl)benzoic acid (7.7 g), dichloromethane (100 ml), oxalyl chloride (2.74 ml) and DMF (3 drops) was stirred at room temperature for 2 hours. After the solvent was distilled off, dichloromethane (50 ml) was added to the residue. This mixture was added dropwise to a mixture of <strong>[25808-30-4]N-methylaminoacetonitrile hydrochloride</strong> (4.86 g), triethylamine (12.0 ml) and dichloromethane (70 ml), while stirring with ice cooling. This mixture was stirred at room temperature for 12 hours. After the solvent was distilled off, ethyl acetate was added to the residue. The mixture was washed successively with water, dilute hydrochloric acid, sodium hydrogen carbonate and water and then dried, after which the solvent was distilled off, to yield 4,5-dimethyl-2-(2-methylbenzoyl)benzoic acid-N-cyanomethyl-N-methylamide as a colorless oily substance (9.2 g). NMR (200 MHz, CDCl3) ppm: 2.26 (3H, s), 2.35 (3H, s), 2.37 (3H, s), 2.99 (3H, s), 4.47 (2H, s), 7.05-7.40 (6H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; sodium hydrogencarbonate; triethylamine; In dichloromethane; water; N,N-dimethyl-formamide; | Step 1 To a solution of 3-(4-fluorobenzoyl)-2-pyridinecarboxylic acid (19.8 g) in dichloromethane (200 ml) were added thionyl chloride (29.1 ml) and DMF (one drop). The mixture was stirred for 4 hours at room temperature. The solvent was distilled off, and the residue was dissolved in dichloromethane (100 ml). This solution was added to a mixture of <strong>[25808-30-4]N-methylaminoacetonitrile hydrochloride</strong> (9.46 g), triethylamine (33.7 ml) and dichloromethane (150 ml), which was stirred for 16 hours at room temperature. The solvent was distilled off. To the residue was added water, which was subjected to extraction with ethyl acetate. The extract solution was washed with an aqueous solution of sodium hydrogencarbonate and water, which was then dried, followed by distilling off the solvent to leave N-cyanomethyl-3-(4-fluorobenzoyl)-N-methyl-2-pyridinecarboxamide (22.8 g). NMR(200 MHz,CDCl3) ppm: 3.16(3H*1/3,s), 3.21(3H*2/3,s), 4.44(2H*2/3,s), 4.55(2H*1/3,s), 7.17(2H,t,J=8.4 Hz), 7.50(1H,m), 7.85(3H,m), 8.75(1H,dd,J=1.6,4.8 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In chloroform; water; | 54.5 g of ethyl chloroformate was then poured dropwise into the resulting mix, with the temperature being maintained at between 0° and 5° to form a mixed anhydride. When the addition operation was concluded, agitation was effected for a further period of 30 minutes at 5° C. At the same time, 400 cc of chloroform and 55.5 g of triethylamine were introduced into a one liter balloon flask provided with an agitator and the mixture was cooled in an ice bath. 59 g of <strong>[25808-30-4]methylamino acetonitrile hydrochloride</strong> in finely divided form was then added gradually. The solution thus obtained was then gradually added to the solution of mixed anhydride which was produced previously, with the temperature being maintained at between 5° and 10°. At the end of the addition operation, agitation was effected for a further period of 1 hour at 5°C. The temperature of the reaction mix was permitted to rise and the reaction medium was left overnight. The chloroform was then distilled off under a slight vacuum. The residue was dissolved in water and the last traces of chloroform were removed by entrainment with water. The remaining product crystallized out. A few drops of soda lye were then added to make the medium slightly alkaline and then the product obtained was drained, washed with water until the Cl- ions were removed, and dried at 40°. Weight obtained=92 g MP=128° C. Yield=72.5percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | A. N-Carbethoxy-N-methylaminoacetonitrile Triethylamine (5.2 ml; 37.6 mmoles) was added to a suspension of methylaminoacetonitrile hydrochloride (2.0 g; 18.8 mmoles) in 20 ml of methylene chloride. The resulting suspension was cooled in an ice-bath and a solution of ethyl chloroformate (2.14 g; 19.8 mmoles) in 10 ml of methylene chloride was added over a 0.5 hour period, and the mixture was then heated at reflux temperature for 18 hours. The reaction mixture was evaporated under reduced pressure to give a semi-solid residue which was triturated with diethyl ether and filtered, and the filtrate was evaporated under reduced pressure to yield the title compound as an oil (2.2 g), bp 96°-98°/5.2 mm Hg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | A. N-Carbophenoxy-N-methylaminoacetonitrile To a suspension of methylaminoacetonitrile hydrochloride (100 g; 0.94 mole) in 1 liter of methylene chloride (cooled in an ice-water bath) was added triethylamine (260 ml, 1.88 moles) and a solution of phenyl chloroformate (155.0 g; 0.99 mole) in 500 ml of methylene chloride. The reaction mixture was heated at reflux temperature for 18 hours, then evaporated under reduced pressure to give a semi-solid which was triturated with 1 liter of diethyl ether and filtered. The filtrate was evaporated under reduced pressure and the residual oil was vacuum distilled to yield the title compound (123 g), bp 111°-113°/0.25 mm Hg; the NMR spectrum (60 MHz) in CDCl3 gave the following resonances delta: 7.23 (m, 5H); 4.30 (s, 2H); 3.13 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; triethylamine; In ethanol; chloroform; water; | EXAMPLE 8 3-Amino-1,4,5-trimethyl-1H-pyrrole-2-carbonitrile 10.3 ml (0.74 mole) of triethylamine, 7.2 g (0.74 mole) of 3-cyanobutan-2-one and 0.5 g of p-toluenesulfonic acid are successively added to a suspension of 7.8 g (0.74 mole) of <strong>[25808-30-4]N-methylaminoacetonitrile hydrochloride</strong> in 70 ml of chloroform, and the mixture is boiled for 5 hours, using a water separator. After it has been boiled, the mixture is washed twice with 10 ml of water each time and dried over sodium sulfate; the solvent is then stripped off in vacuo. In order to remove all of the chloroform, the residue is twice taken up in 100 ml (each time) of dry ethanol, and the mixture concentrated each time in vacuo. The resulting oil is warmed (bath temperature of 50° C.) in 100 ml of 1 N sodium ethylate/ethanol for 2 hours; some of the ethanol is removed. The mixture is then taken up in 100 ml of water and extracted several times with methylene chloride. After being dried over sodium sulfate and concentrated on a rotary evaporator, the extracts yield a solid residue, which is recrystallized from diisopropyl ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride;aluminium trichloride; In ethanol; nitrobenzene; Petroleum ether; | A. At 0° C., 1.7 g of methylaminoacetonitrile hydrochloride and 3.0 g of 7-hydroxyindole-2-carboxylic acid methyl ester are added to a solution of 8.4 g of aluminum chloride in 30 ml of nitrobenzene. Then gaseous hydrogen chloride is introduced into the thus-obtained solution at -4° to -2° C. for 6 hours, whereafter the reaction mixture is stirred for 16 hours at the same temperature, poured into ice water, agitated for another 10 minutes, and the precipitate is vacuum-filtered and discarded. The filtrate is combined with petroleum ether, the precipitate is vacuum-filtered, extracted by boiling with ethanol, and vacuum-filtered to remove it from the undissolved matter. Yield: 1.1 g of 4-methylaminoacetyl-7-hydroxyindole-2-carboxylic acid methyl ester hydrochloride, decomposition point 255°-256° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; | EXAMPLE 1 (N-Methyl-3-Trifluoromethylbenzylsulfonamido)Acetonitrile In this example 36.1 g of 3-trifluoromethylbenzylsulfonyl chloride was added cautiously to a solution containing 29.8 g of the hydrochloride salt of methylaminoacetonitrile and 38.7 g of potassium carbonate in 130 ml of water at room temperature. The reaction mixture was maintained at about 70° C. for about four hours. The mixture was allowed to cool and then extracted with ethyl ether. The ethyl ether extract was dried over magnesium sulfate and evaporated to dryness. The residue was vacuum filtered through silica gel using 3percent vol. tetrahydrofuran: chloroform as eluent. 29 g of the title compound was obtained as a waxy white solid. | |
With pyridine; hydrogenchloride; triethylamine; In dichloromethane; water; | EXAMPLE 6 (N-Methyl-3-trifluoromethylbenzylsulfonamido)acetonitrile In this example 21 ml (0.15 mole) of triethylamine was added over a 5 minute period to a cooled solution containing 16 g (0.15 mole) of the hydrochloride salt of methylaminoacetonitrile in 150 ml of methylene chloride. The mixture was stirred at 20° C. for 15 minutes and then 7.9 g (0.1 mole) of pyridine was added. Then 25.9 g (0.1 mole) of 3-trifluoromethylbenzylsulfonylchloride dissolved in about 50 ml methylene chloride was added to the reaction mixture. The reaction mixture was maintained at 20° C. during the addition and then refluxed for three hours. The mixture was cooled to room temperature and washed once with 200 ml of water and then washed twice with 100 ml of aqueous 5 wt. percent hydrochloric acid. The washed mixture was dried over magnesium sulfate and evaporated under vacuum affording 28.2 g of the title compound as a solid residue. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In dichloromethane; water; | EXAMPLE 3 Preparation of N-cyanomethyl, N-methyl-2-phenoxybenzamide 2.7 parts of methylaminoacetonitrile hydrochloride was added to a solution of 2 parts of sodium hydroxide in 25 parts of water at ~15°. When the addition was complete a solution of 5.8 parts of 2-phenoxybenzoyl chloride in 50 parts of methylene chloride was added dropwise. The mixture was stirred vigorously for 5 hrs. at ~20°. The methylene chloride layer was then separated, washed with water and dried over magnesium sulfate. Removal of the magnesium sulfate by filtration and concentration of the filtrate gave 4.6 parts of N-cyanomethyl-N-methyl-2-phenoxybenzamide as a viscous oil. NMR (CDCl3) 3delta(S,3H,CH3), 4.1delta,4.3delta (2S,2H,CH2), 7.05delta, (m,9H,Aromatic H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N,N-dimethyl-formamide; at 90℃; for 3h; | Example 109(4S,5R)-3-(4-(4-chlorophenoxy)phenyl)-5-(chloromethyl)-4-(3-fluorophenyl)oxazolidin-2- one; [00174] To a solution of the mesylate, prepared using the methods described in example34 (35 mg, 0.07 mmol) and triethylamine (0.125 mL, 0.9 mmol) in DMF (0.3 mL) was added methylaminoacetonitrile hydrochloride (76 mg, 0.7 mmol). The reaction was heated to 90 °C and stirred for 3 h. After cooling, and dilution with water and ethyl acetate, the organic was washed successively with 1 M HCl, brine, dried over magnesium sulfate, filtered and concentrated. HPLC purification (0-90percent acetonitrile/water) gave 16 mg (53percent) of the title compound as a colorless oil. 1H NMR (acetone-d6) delta (ppm) 7.52-7.56 (m, 2H), 7.47 (ddd, IH, J = 8.1, 8.1, 6.0 <n="87"/>Hz), 7.31-7.42 (m, 4H), 7.10-7.15 (m, IH), 6.95-6.99 (m, 4H), 5.55 (d, IH, J = 4.8 Hz), 4.75 (q, IH, J = 4.4 Hz), 4.10-4.17 (m, 2H). HPLC-MS calculated C22Hi6Cl2FNO3 (M+H+): 432.1, found: 432.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | b) Preparation of intermediate [58.3] Intermediate (82 (0.0094 mol) was added at room temperature to CH2Cl2 (70ml). Et3N (0.0188 mol) was added. 1,1'-carbonylbis-1H-in-imidazole (0.0188 mol) was added. The mixture was stirred at room temperature for 4.5 hours. (Methylamino)acetonitrile .HCl (0.0188 mol) was added. The mixture was stirred at room temperature for 12 hours. The organic layer was separated, washed twice with water, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 98.5/1.5; 35-70 mum). The pure fractions were collected and the solvent was evaporated. The residue (2.2g) was crystallized from CH3CN. The precipitate was filtered off and dried, yielding: 1.5g of intermediate (83) (41 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In a vessel load: 120 g of nitrobenzene and 53.3 g of aluminium chloride making attention to the exothermic effect, then 21.2 g of methylaminoacetonitrile hydrochloride were added. Then 27.1 g of veratrole and 0.6 g of anisole were poured into the mixture. In a few minutes a homogeneous solution was obtained, then hydrochloric acid was bubbled through the solution vigorously for 6 hrs at a temperature of 25° C.The mixture was then poured into 320 ml of water under cooling. Then the organic layer was separated at 75° C. and the aqueous layer underwent to vacuum distillation (50 ml are distilled off) in order to remove the latest traces of solvent. The obtained aqueous layer was then treated with 4.9 g of decolorizing charcoal for 1 hr at 80° C. Then the charcoal was filtered off and the panel washed with 50 ml of water which were joined together with the mother liqueur. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The amino-nitrile (1 mmol) is dissolved in dry CH2Cl2 (5 mL) to which is added benzene (2 mL). With stirring, triflic acid (2 mL) is then slowly added and the reaction mixture is stirred overnight at 60-80 °C. The mixture is then quenched by pouring the solution over ice/water. The aqueous solution is then made basic by slow addition of 10 M NaOH and the solution is extracted twice with chloroform. The organic layer is washed with water, brine (2.x.20 mL) and dried over anhydrous sodium sulfate. In the event that imine/ketone mixtures are obtained, it may be necessary to stir the triflic acid/ice/water mixture for few hours in order to ensure complete hydrolysis. The products are purified via column chromatography (silica gel; hexanes/ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 122-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(cyanomethylmethyl-carbamoyl)-ethyl]-amide2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(cyanomethylmethyl-carbamoyl)-ethyl]-amide.Prepared according to the procedure outlined in Example 11 substituting Boc-D-alanine for Boc-D-leucine monohydrate and methylaminoacetonitrile hydrochloride for dimethylamine hydrochloride. MS: (M+H)+=327. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With sodium cyanide; In methanol; water; at 20 - 70℃; | Example 15 1-(7-Chloroisoquinolin-3-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (37)To a stirred solution of <strong>[25808-30-4]2-<strong>[25808-30-4](methylamino)acetonitrile hydrochloride</strong></strong> (4.17 g, 39.13 mmol) in CH3OH/H2O (45 mL, 2:1 v/v) was added NaCN (2.1 g, 42.68 mmol), and the reaction mixture was maintained at RT for 5 min. To the above solution, 4-chlorobenzaldehyde (5.0 g, 35.56 mmol) in CH3OH (30 mL) was added slowly dropwise at the same temperature for 20 min, then the temperature was gradually increased to 70° C. and maintained for 8 h. After completion of reaction (monitored by TLC, 20percent EtOAc/hexanes), the reaction was quenched with H2O (20 mL) and extracted with EtOAc (3.x.100 mL). The combined extracts were washed with H2O (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with 15-20percent EtOAc gradient in hexanes) to yield Y (4.0 g, 18.21 mmol, 51percent) as a thick syrup. 1H NMR (500 MHz, CDCl3): delta 7.48 (d, J=8.7 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 4.86 (s, 1H), 3.47 (d, J=14.0 Hz, 1H), 3.45 (d, J=14.0 Hz, 1H), 2.51 (s, 3H). MS (ESI): m/z 218 [M-H]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In acetonitrile;Inert atmosphere; Reflux; | General procedure: A dry one neck 50mL round bottom flask equipped with magnetic stirring, reflux condenser, and nitrogen atmosphere (or drying tube) was charged with the vinamidinium salt (3.30 mmol), methylaminoacetonitrile hydrochloride (0.355 g, 3.33mmol) and triethylamine (0.97 mL, 6.95 mmol).Anhydrous acetonitrile (10 mL) was added and the mixture was allowed to stir at reflux overnight. The flask wascooled to room temperature and the volatiles were removed in vacuo. The remainingsolid was partitioned between water and ethyl acetate. The ethyl acetate layer was dried over sodiumsulfate and concentrated in vacuo togive the crude solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | [Example 50] Preparation of 3-methyl-1-(4-methylbenzyl)-4-(4-phenoxyphenyl)iminoimidazolidine-2-one (I-363) To a mixture of 4-methylbenzylamine hydrochloride (10 g, 83 mmol) and N,N-dimethylacetamide (50 mL) was added 1,1'-carbonyldiimidazole (14.05 g, 87 mmol) under ice-cooling. To the mixture was added DBU (18.66 mL, 124 mmol), and the resulting mixture was stirred at 0°C for 30 minutes. To the reaction mixture was added <strong>[25808-30-4]2-<strong>[25808-30-4](methylamino)acetonitrile hydrochloride</strong></strong> (10.55 g, 99 mmol) under ice-cooling. Further, to the mixture was added DBU (24.88 mL, 165 mmol) under ice-cooling, and the resulting mixture was stirred at room temperature for 45 minutes and stirred at 50°C for additional 90 minutes. To the reaction mixture was added water (500 mL). The mixture was extracted with ethyl acetate (500 mL*2), washed by brine (500 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (methanol/chloroform) to give 4-imino-3-methyl-1-(4-methylbenzyl)imidazolidine-2-one (9.43 g, Yield:52percent) as yellow solid. 1H-NMR (delta ppm TMS/CDCl3): 2.31 (3H, s), 2.94 (3H, s), 3.93 (2H, s), 4.66 (2H, s), 6.90 (1H, br.s), 7.11 (2H, d, J=8.2 Hz), 7.27 (2H, d, J=8.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In dichloromethane; N,N-dimethyl-formamide; at 0 - 55℃; for 16h; | To a suspension of <strong>[25808-30-4]methylamino acetonitrile hydrochloride</strong> (20 g, 142.0 mmol) in DCM (1300 ml), was added oxalyl bromide (54 ml, 188.67 mmol) followed by slow addition of DMF (1.5 ml) at 0°C. The reaction mixture was stirred at 55°C for 16 h. DCM was concentrated under reduced pressure, the residue obtained was purified by column chromatography by eluting with 2percent MeOH/CH2Cl2 to afford the desired compound as a pale yellow solid (34 g, 92 percent); *H NMR (400MHz, DMSO-dg) delta 8.1 (s, 1H), 3.4 (s, 3H). LC-MS: 268.9 (M+l)+. |
92% | In dichloromethane; N,N-dimethyl-formamide; at 0 - 55℃; for 16h; | To a suspension of <strong>[25808-30-4]methylamino acetonitrile hydrochloride</strong> (20 g, 142.0 mmol) in DCM (1300 mL), was added oxalyl bromide (54 mL, 188.67 mmol) followed by slow addition of DMF (1.5 mL) at 0°C. The reaction mixture was stirred at 55°C for 16 h. DCM was concentrated underreduced pressure, the residue obtained was purified by colunm chromatography by eluting with2percent MeOH/CH2C12 to afford the desired compound as a pale yellow solid (34 g, 92percent); 1H NMR(400 MHz, DMSO-d6) oe 8.1 (s, 1H), 3.4 (s, 3H). LC-MS: 268.9 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | A 5-L three-neck RBF equipped with a mechanical stirrer, thermoregulator, reflux condenser andnitrogen inlet was charged with compound 5(181.0 g, 1.66 mol) and anhydrous DCM (1.5 L). Oxalyl bromide (367 g, 1.70 mol) wasadded and the stirring suspension was heated to reflux for 18 h (Caution: poisonous gas evolution). The reaction mixture was then cooled to 0 °C in an ice/water bath before anhydrous DMF (186 g, 2.55 mol) was slowly added (Caution: reaction was exothermic andfoaming with poisonous gas evolution). Dueto the exothermic nature of the reaction, mixture temperature rose to 12°C. Additional oxalyl bromide (550 g,2.55 mol) was added portion-wise (Caution: reaction was exothermic withpoisonous gas evolution). The mixturetemperature rose further to 16 °C. Afterthe addition, the reaction mixture was stirred in a cooling bath for 20 min andat 25 °C for 30 min and was heated to reflux for 18 h. Upon cooling to 25 °C, the reaction mixturewas poured into a 2.5 gal. carboy containing saturated aqueous sodiumbicarbonate (2 L) (Caution:foaming). Sodium bicarbonate (~405 g)was added portion-wise to adjust thepH to 8 (Caution: foaming). After separation, the aqueous layer wasextracted with DCM (3 × 1 L). Thecombined organic layers were dried over sodium sulfate, filtered andconcentrated under vacuum. The resultingresidue suspended in DCM (approximately 250 mL) was purified on a silica gelplug (glass frit, 6? diameter, 2.5? height of silica) and eluted with methylenechloride (approximately 5 L total). After evaporation, the desired product VI (317.2 g, 71percent) was obtained as a light reddish-brown solid (mp: 94?95 C); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27.5 mg | With 2-picoline borane complex; In methanol; at 20℃; for 3h; | REFERENCE SYNTHETIC EXAMPLE 41 2-(Methyl[trans-4-(3-methyl-4-oxo-7-[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahvdro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-1-yl)cyclohexyl]methyl}amino)acetonitrile To a solution of trans-4-(3-methyl-4-oxo-7-[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-1-yl)cyclohexanecarbaldehyde (25 mg, 0.056 mmol) obtained in Reference Synthetic Example 29 in methanol (0.5 mL), methylaminoacetonitrile hydrochloride (7.8 mg, 0.073 mmol) and 2-picoline borane (8.1 mg, 0.073 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was mixed with 1 M aqueous sodium hydroxide and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin-layer chromatography (ethyl acetate/2-propanol=9/1 (v/v)) to obtain the title compound as a colorless oil (27.5 mg, yield: 99percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | EXAMPLE 50 Preparation of 3-methyl-1-(4-methylbenzyl)-4-(4-phenoxyphenyl)iminoimidazolidine-2-one (I-363) To a mixture of 4-methylbenzylamine hydrochloride (10 g, 83 mmol) and N,N-dimethylacetamide (50 mL) was added 1,1'-carbonyldiimidazole (14.05 g, 87 mmol) under ice-cooling. To the mixture was added DBU (18.66 mL, 124 mmol), and the resulting mixture was stirred at 0° C. for 30 minutes. To the reaction mixture was added <strong>[25808-30-4]2-<strong>[25808-30-4](methylamino)acetonitrile hydrochloride</strong></strong> (10.55 g, 99 mmol) under ice-cooling. Further, to the mixture was added DBU (24.88 mL, 165 mmol) under ice-cooling, and the resulting mixture was stirred at room temperature for 45 minutes and stirred at 50° C. for additional 90 minutes. To the reaction mixture was added water (500 mL). The mixture was extracted with ethyl acetate (500 mL*2), washed by brine (500 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (methanol/chloroform) to give 4-imino-3-methyl-1-(4-methylbenzyl)imidazolidine-2-one (9.43 g, Yield: 52percent) as yellow solid. 1H-NMR (delta ppm TMS/CDCl3): 2.31 (3H, s), 2.94 (3H, s), 3.93 (2H, s), 4.66 (2H, s), 6.90 (1H, br.s), 7.11 (2H, d, J=8.2 Hz), 7.27 (2H, d, J=8.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; at 20℃; for 24h;Inert atmosphere; | General procedure: [0038] To the starting compound (carboxyalkyl psoralen, 0.05?0.50 g, 1 .0 mol. equivalent), <strong>[25808-30-4]N-methylaminoacetonitrile hydrochloride</strong> or aminoacetonitrile hydrochloride (1.25 mol. equivalent), THE (10?15 mL), EDC (1 .25 mol. equivalent), and Et3N (1 .25 mol. equivalent) were added under argon atmosphere. The resulting suspension was stirred at room temperature for 24 h. Then, the solvent was evaporated under reduced pressure. To the resulting residue, 1 M HCI (20? 50 mL) and EtOAc (20?50 mL) were added, transferred to a separating funnel, shaken intensively and left to allow the separation of the layers. The aqueous layer was further extracted with EtOAc (4 x 20?70 mL). The combined organic phases were dried over Na2SO4, filtered, and evaporated under reduced pressure. The crude products were subsequently purified by crystallization or column chromatography. [0113] The title compound was prepared from 2-(3-(4-bromophenyl)-5-methyl-7-oxo-7H-furo[3,2-g]chromen-6-yl)acetic acid (0.072 g) and N-methylaminoacetonitrilehydrochloride following the general procedure C (synthesis of N(cyanomethyl)amides). The compound was purified by column chromatography(MP = EtOAc).[0114] Appearance: white amorphous solid, m = 0.017 g; Yield: 15percent; Melting point:230?234 °C; ESI-MS [M-H]: 463; HRMS: (m/z = 463) for C23H16N2O4Br: calculated463.0293, found 463.0290; 1H NMR (400 MHz, DMSO-d6) oe (ppm) = 2.51 (5, 3H,Ar-CH3), 3.24 (5, 3H, NCH3), 3.83 (5, 2H, CH2CO), 4.43 (5, 2H, CH2CN), 7.72-7.75(m, 2H, Ar-H), 7.79-7.83 (m, 2H, Ar-H), 7.84 (5, 1 H, Ar-H), 8.21 (5, 1 H, Ar-H), 8.55(5, 1H, Ar-H); IR (ATR): 3619, 2535, 2160, 2029, 1976, 1693, 1581, 1465, 1392,1160, 1114,1071,880,861,834,792 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; | 3.104. Compound 98: N-Cyanomethyl-3-ethyl-5-fluoro-4-({4-[((lR,2R)-2-fluoro- cyclopropanecarbonyl)-aminoJ-l-methyl-lH midazof4,5-cJpyridin-6-yl}-methy benzamide 3.104.1. Step i): 4-[4-(Benzhydrylidene-amino)-l-methyl-lH-imidazo[4,5-c]pyridin-6-yl]- methyl-amino}-N-cyanomethyl-3-ethyl-5-fluoro-N-methyl-benzamide To the carboxylic acid (1 eq, 200 mg) and triethylamine (12 eq, 0.65 mL) in DMF (2 mL), is added HATU (1.5 eq, 222 mg) and <strong>[25808-30-4]methylamino-acetonitrile hydrochloride</strong> (4 eq, 166 mg). The resulting mixture is stirred overnight at room The reaction is diluted with DCM and water, passed through a phase separator and concentrated to afford the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 70℃; for 24h; | To a suspension ofcompound 18 (147 mg, 0.67 mmol) in1,2-dichloroethane (8 mL), methylaminoacetonitrile hydrochloride (79mg, 0.74 mmol) was added at room temperature. After 5 min, DIPEA (130 muL, 0.74mmol) was added, followed by the slow addition of Na(OAc)3BH (185mg, 0.87 mmol). The reaction mixture was then heated to 70 °C and left to stirat that temperature for 24 h. Then, CH2Cl2 (10 mL) wasadded and the mixture extracted with saturated aqueous solution of NaHCO3(20 mL). The aqueous phase was further washed with CH2Cl2(2× 50 mL), the combined organic layers were dried with anhydrous Na2SO4,filtered, and evaporated under reduced pressure. The crude product was purifiedby flash column chromatography using CH2Cl2/MeOH/NH4OH= 10/1/0.1 as an eluent, to yield 80 mg (44percent) of yellow solid. Mp 116.0?117.0 °C;Rf = 0.23 (CH2Cl2/MeOH/NH4OH= 3/1/0.1); 1H NMR (400 MHz, DMSO-d6) delta 2.32 (s, 3H, CH3),3.87 (s, 2H, CH2CN), 3.95(s, 2H, CH2N), 7.17 (d, J = 8.9 Hz, 1H, Ar-H), 7.89 (d, J = 9.0 Hz,1H, Ar-H), 8.50 (d, J = 8.9 Hz, 1H, Ar-H), 9.13 (d, J = 9.0 Hz,1H, Ar-H), 11.28 (br s, 1H, OH);1H NMR (400 MHz, CDCl3) delta 2.51 (s, 3H, CH3), 3.60 (s, 2H, CH2CN),4.00 (s, 2H, CH2N), 7.22(d, J = 8.8 Hz, 1H, Ar-H), 7.88 (d, J = 8.9 Hz, 1H, Ar-H),8.59 (d, J = 8.8 Hz, 1H, Ar-H), 9.34 (d, J = 8.9 Hz, 1H, Ar-H),resonance for OH missing; 13C NMR (100 MHz, DMSO-d6) delta 41.35, 44.98, 61.32, 110.07, 115.81, 121.69,124.56, 128.52, 132.92, 135.16, 136.70, 157.79, 160.34; HRMS (ESI) m/z calculated for C11H13N4O3 [M+H]+ 273.0988, found 273.0986; HPLC purity, 95.51percent, tR = 8.66 min. |
Tags: 25808-30-4 synthesis path| 25808-30-4 SDS| 25808-30-4 COA| 25808-30-4 purity| 25808-30-4 application| 25808-30-4 NMR| 25808-30-4 COA| 25808-30-4 structure
[ 6011-14-9 ]
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[ 4535-90-4 ]
2-Chloro-N-methylethanamine hydrochloride
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[ 326888-32-8 ]
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[ 6011-14-9 ]
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P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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