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CAS No. : | 63139-97-9 |
Formula : | C5H8N2S |
M.W : | 128.20 |
SMILES Code : | CC1=NC=C(CN)S1 |
MDL No. : | MFCD02853614 |
InChI Key : | XYRSJQNUWZHRBX-UHFFFAOYSA-N |
Pubchem ID : | 19046689 |
GHS Pictogram: | ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H315-H318-H335 |
Precautionary Statements: | P261-P280-P301+P310-P305+P351+P338 |
Class: | 8(6.1) |
UN#: | 2923 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
61% | Suspend 2- (2-METHYLTHIAZOL-5-YLMETHYL) ISOINDOLE-1, 3-dione (210 MG, D. 814 mmol) in 6N HCl (8 mL) and heat at reflux for 2.5 hours. Cool to room temperature and stir for an additional 5 hours. Basify the mixture with 2 N sodium hydroxide, extract with methylene chloride (3 x 50 mL), dry (sodium sulfate), filter, and concentrate to afford 70 mg (61% yield) of the title compound as a brown OIL. H NMR (CDC13) 6 7.34 (s, 1H), 4.11 (s, 2H), 2.45 (S, 3H), 1.70 (br s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 85℃; for 4h;Inert atmosphere; | To the solution of 4-bromo-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one (made according to Example 1, by replacing ((1S,2S)-2-( 5-methylpyridin-2-yl)cyclopropyl)methanol with ((I S,2S)-2-(1-methyl-1H -pyrazol-3-yl)cyclopropyl)methanol, 27 mg, 0.08 mmol) in toluene (2 mL) under N2, <strong>[63139-97-9](2-methylthiazol-5-yl)methanamine</strong> (13 mg, 0.096 mmol), Pd2(dba)3 (7 mg, 0.008 mmol), BINAP (7 mg, 0.012mmol) and Na01Bu (9 mg, 0.096 mmol) were added. After the reaction mixture was stirred at 85C for 4 h, 15 mL water was added. The mixture was extracted with EtOAc (3 x 10 mL). Thecombined organics were dried over MgS04, filtered and concentrated in vacuo. The residue was5 purified by reverse phase chromatography (X bridge Prep C180BD, 40-60% acetonitrile inwater with 10 mmol NH4HC03 modifier) to afford the title compound as an oil. 1H NMR (400MHz, MeOD) o 7.56 (s, 1H),7.42 (d, 1H), 5.96 (d, 1H), 5.89 (s, 1H), 4.59 (s, 2H), 4.15-5.11(m, 1H), 4.04-4.01 (m, 1H), 3.81 (s, 3H), 3.63 (s, 3H), 2.66 (s, 3H), 1.95- 1.89 (m, 1H), 1.61-1.53 (m, 1H), 1.01-0.95 (m, 2H); LRMS m/z (M+H) 387.1 found, 387.15 required. | |
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 85℃; for 4h;Inert atmosphere; | Step A: 2-methyl-6-(((lS.2S -2-(l-methyl-lH-pyrazol-3-yl cvclopropyl methoxyN)-4-((2-methylthiazol-5- ylN)methylaminoN)pyridazin-3(2HN)-oneTo the solution of 4-bromo-2-methyl-6-(((lS,2S)-2-(l-methyl-lH-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one (made according to Example 1, by replacing ((lS,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methanol with (( 1 S,2S)-2-(l -methyl- 1 H-pyrazol-3 - yl)cyclopropyl)methanol, 27 mg, 0.08 mmol) in toluene (2 mL) under N2, (2-methylthiazol-5- yl)methanamine (13 mg, 0.096 mmol), Pd2(dba)3(7 mg, 0.008 mmol), BetaGammaNuAlphaRho (7 mg, 0.012 mmol) and NaO'Bu (9 mg, 0.096 mmol) were added. After the reaction mixture was stirred at 85 C for 4 h, 15 mL water was added. The mixture was extracted with EtOAc (3 x 10 mL). The combined organics were dried over MgS04, filtered and concentrated in vacuo. The residue was purified by reverse phase chromatography (X bridge Prep C180BD, 40-60% acetonitrile in water with 10 mmol NH4HCO3modifier) to afford the title compound as an oil. NMR (400 MHz, MeOD) delta 7.56 (s, 1H),7.42 (d, 1H), 5.96 (d, 1H), 5.89 (s, 1H), 4.59 (s, 2H), 4.15 - 5.1 1 (m, 1H), 4.04 - 4.01 (m, 1H), 3.81 (s, 3H), 3.63 (s, 3H), 2.66 (s, 3H), 1.95 - 1.89 (m, 1H), 1.61 - 1.53 (m, 1H), 1.01- 0.95 (m, 2H); LRMS m/z (M+H) 387.1 found, 387.15 required. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: 5.1.5 2-(1-(4-Fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (7a) To a solution of 6a (2.00 g, 5.98 mmol), EDCI (1.50 g, 7.82 mmol) and iPr2NEt (2.67 mL, 15.64 mmol) in N,N-dimethylformamide (80 mL) was added HOBt (1.00 g, 7.40 mmol). The reaction mixture was stirred at ambient temperature for 15 min, followed by addition of 3-(aminomethyl)pyridine (0.73 mL, 7.16 mmol). After stirring for 17 h at ambient temperature, the reaction mixture was diluted with ethyl acetate (300 mL) and sequentially washed with water, saturated NaHCO3 solution, water and brine. The organic solution was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was crystallized from ethyl acetate and hexanes to yield 7a as an off-white solid (1.93 g, 76%), mp 178-180 C (ethyl acetate/hexanes); By a similar procedure as described for 7a, 7i was obtained as an off-white solid (0.18g, 68%). Mp 176-177C (ethyl acetate/hexanes); 1H NMR (300MHz, CDCl3) delta 8.25 (s, 1H), 7.41-7.31 (m, 2H), 7.07-6.97 (m, 3H), 6.49 (t, J=5.3Hz, 1H), 4.97 (s, 2H), 4.62 (d, J=5.3Hz, 2H), 2.70 (s, 3H), 2.64 (s, 3H); MS (ES+) m/z 445.1 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With triphenylphosphine; In tetrahydrofuran; water; at 0 - 20℃; for 16h; | To a stirred solution of compound 66 (2.3 g, 14.93 mmol) in THF: H20 (5: 1, 80 mL) was added triphenyl phosphine (7.8 g, 29.87 mmol) at 0 C; warmed to RT and stirred for 16 h.The reaction was monitored by TLC; after completion of the reaction, the volatiles wereremoved in vacuo to obtain the crude, which was triturated with diethyl ether (20 mL) to afford amine (900 mg, 47%) as a colorless syrup. TLC: 10% MeOH/ CH2C12 (Rf: 0.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; In 1,4-dioxane; dichloromethane; at 0 - 20℃; for 3h;Inert atmosphere; | To a stirred solution of compound 66 (2.3 g, 14.93 mmol) in THF: H20 (5: 1, 80 mL) was added triphenyl phosphine (7.8 g, 29.87 mmol) at 0 C; warmed to RT and stirred for 16 h.The reaction was monitored by TLC; after completion of the reaction, the volatiles wereremoved in vacuo to obtain the crude, which was triturated with diethyl ether (20 mL) to afford amine (900 mg, 47%) as a colorless syrup. TLC: 10% MeOH/ CH2C12 (Rf: 0.2).The above compound was dissolved in CH2C12 (10 mL) added 4 N HC1 in 1, 4-dioxane (5 mL) under inert atmosphere at 0 C; warmed to RT and stirred for 3 h. The volatileswere removed in vacuo to obtain the crude, which was triturated with EtOAc (2 mL), diethyl ether (2 mL) to afford compound 67 (1.1 g, 95%) as an off-white solid. TLC: 10% MeOHJCH2C12 (Rf: 0.2); ?H NMR (DMSO-d6, 500 MHz): oe 8.59 (br. s, 3H), 7.74 (s, 1H), 4.23 (q, J = 5.6 Hz, 2H), 2.66 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | General procedure: To a solutionof the corresponding aldehyde (1.2 eq.; unless stated otherwise) in DMF (2 inL per 0.3 mmol of aldehyde; unless stated otherwise) was added the corresponding amine (2.5 eq.; unless stated otherwise) and the resulting solution was stirred at 25 C to form the corresponding inline. Then, the corresponding isocyano(tosyl)methyl)arene reagent (1 eq.; unless stated otherwise) and K2CO3 (1.5 eq.; unless stated otherwise*) were added and the reaction mixture was stirred at 25 C (unless stated otherwise). The reaction was stopped after the time indicated for each particular reaction. The reaction progress was monitored by TLC. (0083) A saturated aqueous solution of NH4CI (10 mL per 1 mmol of aldehyde) was added to the reaction mixture, which was then extracted with EtOAc (2 x 30 mL per 1 mmol of aldehyde). The combined organic extracts were washed with H2O (2 x 25 mL per 1 mmol of aldehyde), dried over MgSCC, filtered, and the solvent was evaporated in vacuo to provide the crude product. The residue obtained after the workup was purified using column chromatography or preparative TLC (unless stated otherwise). (0084) * note: in cases when the amine was used as HC1 salt, 4 eq. of K2CO3 were used |
Tags: 63139-97-9 synthesis path| 63139-97-9 SDS| 63139-97-9 COA| 63139-97-9 purity| 63139-97-9 application| 63139-97-9 NMR| 63139-97-9 COA| 63139-97-9 structure
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