Structure of 89799-34-8
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CAS No. : | 89799-34-8 |
Formula : | C3H9ClN2O |
M.W : | 124.57 |
SMILES Code : | CC(O)C(N)=N.[H]Cl |
MDL No. : | MFCD26937570 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
99% | In ethanol; | Step B. 2-hydroxy-propionamidine hydrochloride A suspension of 2-hydroxypropionimidic acid ethyl ester hydrochloride (prepared according to the method of Preparation One, Step A, 751 g, 4.87 mol) in ethanol (3.75 L) at 0 C. was saturated with ammonia gas maintaining the internal temperature below 5 C. for 1 h. It was then stirred at ambient temperature for 18 h. The solid was filtered off and dried under vacuum at 40 C. to obtain a solid. The filtrate was concentrated to one half its volume and a second crop of solid was collected which was dried under vacuum and combined with the fist crop to afford 2-hydroxy-propionamidine hydrochloride as a yellow solid (608 g, 99%); mp, 134-138 C.; 1H NMR (DMSO-d6, 300 MHz) delta1.33 (t, 3H), 4.42(q, 1H), 6.25-6.88 (bs, 1H), 8.72-9.25 (bs, 3H). |
In ethanol; | Step B: 2-Hydroxy-propionamidine hydrochloride A suspension of 2-hydroxypropionimidic acid ethyl ester hydrochloride (prepared according to the method of Preparation Twelve, Step A, 751 g, 4.87 mol) in ethanol (3.75 L) at 0 C. was saturated with ammonia gas, maintaining an internal temperature <5 C., for 1 h then stirred at ambient temperature for 18 h. The solid was filtered off and dried under vacuum at 40 C. to give an initial crop of material. The filtrate was concentrated to one-half volume and a second crop was collected and dried under vacuum. The first and second crops were combined to give the title compound of Preparation Twelve, Step B as a yellow solid, 608 g (99%). mp: 134-138 C.; 1H NMR (DMSO-d6, 400 MHz) delta1.30 (d, 3H), 4.38 (q, 1H), 6.23 (br s, 1H), 7.35 (br s, 1H), 8.78 (br s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
232 g (38%) | In diethyl ether; water; | Step D: 2-(1-Hydroxy-ethyl)-3H-pyrimidin-4-one To a solution of ethyl 3-hydroxy-acrylate sodium salt (prepared according to the method of Preparation Twelve, Step C, 1301 g, 9.42 mol) in water (1.3 L) was added a solution of <strong>[89799-34-8]2-hydroxy-propionamidine hydrochloride</strong> (prepared according to the method of Preparation Twelve, Step B, 610 g, 4.9 mol) in water (1.3 L) at ambient temperature and stirred for 48 h. The solution was adjusted to pH 7.0 with acetic acid then continuously extracted with chloroform for 48 h. The extract was dried over sodium sulfate and filtered. The filtrate was concentrated to a solid, slurried in ethyl ether, filtered, and dried to give the title compound as a solid, 232 g (38%). mp: 121-124 C.; 1H NMR (DMSO-d6, 400 MHz) delta1.30 (d, 3H), 4.46 (q, 1H), 5.62 (br s, 1H), 6.13 (d, 1H), 7.80 (d, 1H). |
In diethyl ether; water; | Step D. 2-(1RS-Hydroxy-ethyl)-3H-pyrimidin-4-one To a solution of sodium 2-ethoxycarbonyl ethenolate (prepared according to the method of Preparation One, Step C, 1301 g, 9.42 mol) in water (1.3 L) was added an aqueous solution of <strong>[89799-34-8]2-hydroxy-propionamidine hydrochloride</strong> (prepared according to the method of Preparation One, Step B, 610 g, 4.9 mol) in water (1.3 L) at ambient temperature and stirred for 48 h. The solution was adjusted to pH 7.0 with acetic acid and then continuously extracted with chloroform for 48 h. The extract was dried over sodium sulfate and filtered. The filtrate was concentrated to a solid which was slurried in ethyl ether, filtered and the solid residue dried to give the title compound of Preparation One (232 g, 38%); mp: 121-124 C.; 1H NMR (DMSO-d6, 300 MHz)??1.45 (d, 1H), 4.42(q, 1H), 6.25-6.88 (bs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Compound 15: 1-(4-amin -6-(methylthio)-1 ,3,5-triazin-2-yl)ethanol; Under a nitrogen atmosphere <strong>[89799-34-8]2-hydroxypropanimidamide hydrochloride</strong> (4.97 g) was suspended in dry N,N-dimethylformamide (25 mL) and sodium hydride (1.66 g, 60 wt% in mineral oil) was added in one portion. When gas evolution ceased the white suspension was heated to 65C. After 1 h dimethyl cyanocarbonimidodithioate (6.24 g) was added and the mixture was stirred at 65 C for 18 hours. The reaction mixture was concentrated and triturated with water (200 mL). The resulting precipitate was filtered off, washed with water and the aqueous layer was extracted with 5% methanol indichloromethane (3 x 100 mL). The combined organic extracts were dried (sodium sulfate) and concentrated before being purified by flash chromatography eluting with 10% methanol in dichloromethane to give the title compound (300 mg) as a yellow oil that solidified on standing. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 90℃; for 12.0h; | Preparation of Compound A5:To a stirred suspension of compound A2 (14 g, 39 mmol) and <strong>[89799-34-8]2-hydroxypropanimidamide hydrochloride</strong> (5.65 g, 47 mmol) in CH3CN (100 mL) was added potassium carbonate (16.2 g, 117 mmol). The reaction mixture was heated at 90 C. for 12 h, then cooled to room temperature, poured into ice water, extracted with ethyl acetate (2×50 mL). The organic layer was dried over Na2SO4, filtered and concentrated to afford the compound A5 (2.5 g, yield: 26%) as yellow solid.1H NMR (300 MHz, CDCl3): delta: 8.84 (s, 2H), 7.48 (m, 3H), 7.37 (m, 2H), 5.20 (s, 2H), 4.68 (m, 1H), 3.25 (m, 1H), 1.48 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With potassium carbonate; In acetonitrile; at 90℃; for 12.0h; | [0408] Preparation of compound A5: To a stirred suspension of compound A2 (14 g, 39 mmol) and <strong>[89799-34-8]2-hydroxypropanimidamide hydrochloride</strong> (5.65 g, 47 mmol) in CH3CN (100 mL) was added potassium carbonate (16.2 g, 117mmol). The reaction mixture was heated at 90C for 12h, then cooled to room temperature, poured into ice water, extracted with ethyl acetate (2 x 50 mL). The organic layer was dried over Na2S04, filtered and concentrated to afford the compound A5 (2.5 g, yield: 26%) as yellow solid. [0409] 1H NMR (300 MHz, CDC13): delta: 8.84 (s, 2H), 7.48 (m, 3H), 7.37 (m, 2H), 5.20 (s, 2H), 4.68 (m, 1H), 3.25 (m, 1H), 1.48 (d, 3H). [0410] Preparation of compound A6: A solution of compound A5 (3.50 g, 15.8 mmol) in MeOH (30 mL) was added palladium on charcoal 10% (350 mg) and the mixture was stirred under hydrogen atmosphere for 4h. The solid was filtered off and the filtrate was concentrated to get compound A6 (2.0 g, yield: 98%). [0411] 1H NMR (400 MHz, CDC13): delta: 8.84 (s, 2H), 5.40 (brd, 1H), 4.66 (m, 1H), 3.25 (m, 1H), 1.46 (d, 3H). LCMS Found: 141.1 ([M+l]+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium ethanolate; In N,N-dimethyl-formamide; at 120℃; for 4.5h;Inert atmosphere; | Example 4A 5-(4-Chlorophenyl)-2-({5-[(1RS)-1-hydroxyethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (diastereomeric mixture) Under argon, sodium ethoxide (1.531 g, 21.59 mmol, 96% purity) was added portionwise at room temperature to a solution of 2-{3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazide (4.1 g, 10.80 mmol) and <strong>[89799-34-8]2-hydroxypropanimidamide hydrochloride</strong> (1.480 g, 11.88 mmol) in DMF (110 ml). The reaction mixture was stirred at 120 C. for 4.5 h. After cooling, the reaction mixture was partially concentrated in vacuo and then diluted with ethyl acetate. The resulting mixture was washed with water, and after phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was dried under high vacuum to give 4.90 g (92% purity, 10.42 mmol) of the desired compound as a mixture of diastereomers which was used without further purification. LC/MS [method 1]: Rt=0.82 min; MS [ESIpos]: m/z=433 (M+H)+ 1H NMR (400 MHz, DMSO-d6): delta [ppm] 1.39 (d, 3H), 3.79-3.88 (m, 1H), 3.93-4.02 (m, 1H), 4.24-4.36 (m, 1H), 4.80 (quin, 1H), 4.89-5.00 (m, 2H), 5.73 (d, 1H), 6.93 (d, 1H), 7.58-7.65 (m, 2H), 7.70-7.77 (d, 2H), 13.68 (s, 1H). | |
With sodium ethanolate; In N,N-dimethyl-formamide; at 120℃; for 4.5h;Inert atmosphere; | Under argon, sodium ethoxide (1.531 g, 21.59 mmol, 96% purity) was added portionwise at room temperature to a solution of 2- { 3-(4-chlorophenyl)-5-oxo-4- [(2S)-3,3,3-trifluoro-2-hydroxypropyl]4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazide (4.1 g, 10.80 mmol) and 2-hydroxypropanimid- amide hydrochloride (1.480 g, 11.88 mmol) in DMF (110 ml). The reaction mixture was stirred at 120C for 4.5 h. After cooling, the reaction mixture was partially concentrated in vacuo and then diluted with ethyl acetate. The resulting mixture was washed with water, and after phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases weredried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was dried under high vacuum to give 4.90 g (92% purity, 10.42 mmol) of the desired compound as a mixture of diastereomers which was used without further purification.LC/MS [method 1]: R = 0.82 mm; MS [ESIpos]: mlz = 433 (M+H)?H NMR (400 MHz, DM50-do): oe [ppm] 1.39 (d, 3H), 3.79-3.88 (m, 1H), 3.93-4.02 (m, 1H), 4.24-4.36 (m, 1H), 4.80 (quin, 1H), 4.89-5.00 (m, 2H), 5.73 (d, 1H), 6.93 (d, 1H), 7.58-7.65 (m, 2H),7.70-7.77 (d, 2H), 13.68 (s, 1H). |
Tags: 89799-34-8 synthesis path| 89799-34-8 SDS| 89799-34-8 COA| 89799-34-8 purity| 89799-34-8 application| 89799-34-8 NMR| 89799-34-8 COA| 89799-34-8 structure
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