*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 3473-63-0 |
Formula : | C3H8N2O2 |
M.W : | 104.11 |
SMILES Code : | N=CN.CC(O)=O |
MDL No. : | MFCD00012866 |
InChI Key : | XPOLVIIHTDKJRY-UHFFFAOYSA-N |
Pubchem ID : | 160693 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H317 |
Precautionary Statements: | P261-P280 |
* 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 |
---|---|---|
87% | at 125℃; for 18 h; | [0144] A mixture of 2-amino-5-methoxybenzoic acid (10.0 g, 59.9 mmol), formamidine acetate (12.3 g, 119 mmol) in 80 mL of 2-methoxyethanol was heated at 125 °C for 18 hours. After being cooled to room temperature, the precipitate was collected by filtration, washed twice with 2-methoxyethanol and dried in the vacuum to provide 6-methoxyquinazolin- 4(3H)-one (9.1 g, 87percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | at 130℃; for 18 h; | A mixture of 2-amino-4-nitrobenzoic acid (10.0 g, 54.93 mmol) was refluxed at 130° C. for 18 h in methoxyethanol (50 mL) and formamidine acetate (11.43 g, 109.81 mmol). The clear reaction mixture was cooled to room-temperature to form a yellowish precipitant. The solvent was removed under vacuum, and the precipitant was washed several times with aqueous ammonia (0.01 M). The solid was dried in vacuo to yield 8.9 g (84percent) of a light yellow powder. 1H NMR Data: dmso-d6-ppm (δ); 12.68 (1H), 8.37 (d, 1H), 8.33 (d, 1H), 8.26 (1H) and 8.23 (dd, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | for 16 h; Heating / reflux | To a 1.2 M solution of 5-bromoanthranilic acid (1 equiv) in N,N-dimethylformamide was added formamidine acetate (1 equiv). The mixture was heated to reflux and stirred at this temperature for 16 hours. After this time, the reaction was cooled and NaHCO3 solution (5 percent in H2O) (3 volumes) were carefully added and the mixture stirred vigorously. The resulting <n="113"/>precipitate was collected by filtration and then washed with water (2 X 1 volume) and then t- butyl methylether (2 X 1 volume) before being dried in a vacuum oven to give the desired product which required no further purification.6-Bromo-3H-pyrido[2,3-d]pyriniidin-4-one: (91 percent yield, insert) m/z (LC-MS,ESP):225 [M- H]- R/T = 2.31 minutes) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.7 g | at 120℃; for 36 h; Inert atmosphere | 2-Amino-S -bromonictoinic acid (2 g) and formamidine acetate (3.0 g) were heated at 120 °C in2-methoxyethanol (15 ml) for 36 h under argon. The heterogeneous reaction mixture was diluted with water and filtered. The solid was suction dried to obtain 1.7 g of 6-bromopyrido[2,3- d]pyrimidin-4(3H)-one. ‘H NMR (300 MHz, DMSO-d6) ö 12.70 (s, 1H), 9.01 (d, J= 2.6 Hz, 1H), 8.59 (d, J= 2.6 Hz, 1H), 8.33 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In 2-methoxy-ethanol; for 18h;Heating / reflux;Product distribution / selectivity; | Step (e) 6-Chloro-3H-pyrido [3,4-d] pyrimidin-4-one A 1 L round bottomed flask was charged with 5-amino-2-chloro- isonicotinic acid (69.5 g, 0.40 moles), formamidine acetate (84 g, 0.81 moles, 2 mole equivalents), and 600 mL of methoxyethanol. The resulting solution was heated at reflux for 18 hours. After cooling to 5°C, a precipitate was collected by filtration, washed twice with methoxyethanol, and dried overnight in the vacuum oven at 45°C. The reaction yielded 67 g (92percent total yield) of 6-chloro-3H- pyrido [3, 4-D] PYRIMIDIN-4-ONE as a tan solid that was sufficiently pure by NMR to use in the next reaction. 8H (DMSO) 12.70 (1 H, s), 8.86 (1 H, d), 8. 19 (1 H, s), 7.93 (1 H, d) MS [M+H3+ 182 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.73% | In methanol; at 50 - 60℃; for 6h; | To a slurry of compound 2 (10.0 g, 0.044 mol) and anhydrous potassium carbonate (18.2 g, 0.1317 mol) in acetonitrile (100 ml), 4-(3-chloropropyl)morpholine hydrochloride (10 g, 0.05 mol) was added and refluxed for 2.5 h. The solvent was distilled under reduced pressure to give residue which was diluted with water(60 ml) and extracted with ethyl acetate (100 ml) after completion of reaction. The organic layer was distilled under vacuum and dried to obtain 13.65 g (87.50percent) of the compound 3; m. p. 231-233 °C. 1HNMR (DMSO?d6, 400 MHz): delta 7.62 (s, 1H), 7.31 (s, 1H), 7.07 (s, 1H),3.90 (s, 3H), 3.79 (s, 3H), 4.18 (t, 2H), 4.17 (s, 2H), 4.16 (s, 3H), 2.37 (d,1H), 1.91 (d, 2H). IR (numax, cm-1): 3134, 1695, 1601. The compound 3 (10 g, 0.0282 mol) was hydrogenated using 10percent palladium on carbon (1.0 g) in methanol (100 ml) at 3-4 kg/cm3 atambient temperature for 5 h. After completion of the reaction, the catalyst was removed by filtration. The filtrate was distilled off completely to obtain 8.27 g (90.38percent) of compound 4. Compound 4 (8.0 g, 0.0247 mol) was added to formamidine acetate (2.68 g, 0.0257 mol) in methanol (64 ml) and heated at 50-60 °C for 6 h. The reaction mass was cooled to room temperature and stirred for 3 h after completion of reaction. The resulting solid was filtered, washed with methanol (10 ml) and dried to obtain 6.44 g (81.73percent) of the title compound 1; m. p. 267-269 °C 1HNMR (DMSO?d6, 400 MHz): delta 12.06 (s, 1H), 7.96 (s, 1H), 7.45 (s, 1H),7.12 (s, 1H), 4.11 (t, 2H), 3.91 (s, 3H), 3.58 (t, 4H), 3.58 (t, 4H), 1.92 (t, 1H). HRMS (ESI+): m/z: calcd for C16H22N3O4: 343.1508 [M + Na]+;found: 343.1532. IR (numax, cm-1): 2909, 1639, 1607. |
In methanol; at 50 - 60℃; for 6h; | Step II: preparation of 7-methoxy-6-(3-morpholin-4-ylpropoxy)-3//-quinazolin-4-one; 2-Amino-4-methoxy-5-(3-mophiholin-4-yfpropoxy)benzoic acid methyl ester (4 g) was added to formamidine acetate (1.34 g) in methanol (32 ml) and heated at 50-60 0C for 6 hours. After completion of reaction, the reaction mass was cooled to room temperature and stirred for 3 hours. The resulting solid was filtered, washed with methanol and dried to obtain 3.5 g of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methoxy-ethanol; | A mixture of <strong>[379228-26-9]methyl 2-amino-4,6-dimethoxybenzoate</strong> (16 g), formamidine acetate (24 g) and 2-methoxyethanol (330 ml) was stirred and heated to reflux until all of the starting material had reacted. The mixture was evaporated and the residue was triturated under water (100 ml). The resultant solid was isolated, washed with water and dried under vacuum to give 5,7-dimethoxy-3,4-dihydroquinazolin-4-one (14.5 g); NMR Spectrum : (DMSOd6) 3.82 (s, 3H), 3.86 (s, 3H), 6.5 (s, 1H), 6.7 (s, 1H), 7.9 (s, 1H), 11.7 (br s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | 6-(benzyloxy)-7-methoxyquinazolin-4(3H)-one: Preparation 9 (5 g,18.3 mmol) was mixed with amidine acetate (3.8 g, 36.6 mmol) in ethylene glycol monomethyl ether (25 mL) and the mixture was heated at 13O0C for 24 h. After cooling to room temperature, part of the solvent was removed in vacuo and ammonium hydroxide (5 mL, 30% in water) and water (50 mL) were added. The solid was filtered, was washed with water and hexanes, and was then dried under vacuum to afford 4.87 g (94% yield) of the title compound; MS (AP/CI): 283.1 (M+H)+ . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With N-ethyl-N,N-diisopropylamine; In ISOPROPYLAMIDE; at 80℃; for 0.5h; | Example 4 1-(4-Amino-8-fluoro-quinazolin-7-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one (Compound 4); <strong>[143879-80-5]2,3,4-Trifluoro-benzonitrile</strong> (3.00 g, 19.1 mmol) is mixed with dimethylacetamide (30 mL). Formamidine acetate (1.99 g, 19.1 mmol) and diisopropylethyl amine (10 mL, 57.3 mmol) are added, and the resulting reaction mixture is slowly heated. Upon heating, the starting heterogeneous mixture slowly turns into a homogeneous solution. At 80° C., precipitates start to form. The reaction mixture proceeds at 80° C. for 30 minutes before it is cooled and filtered. The collected solid is further washed with DCM to afford 1.50 g of 7,8-Difluoro-quinazolin-4-ylamine (43percent yield) as white solid. LC/MS found m/z=182 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In ISOPROPYLAMIDE; at 100℃; for 16h; | Example 31 7-Fluoro-pyrido[3,2-d]pyrimidin-4-ylamine; <strong>[298709-29-2]3,5-Difluoro-pyridine-2-carbonitrile</strong> (2.54 mmol, 356 mg) is dissolved in DMA (5 mL) and then formamidine acetate is added (2.54 mmol, 264.6 mg) followed by DIEA (7.62 mmol, 983 mg). The reaction mixture is stirred for 16 h at 100° C., then poured into saturated NH4Cl aq. and extracted 3 times with CH2Cl2. The organics are dried with Na2SO4, concentrated, and purified on Biotage with 0-20percent MeOH in CH2Cl2. This gives the desired product 7-Fluoro-pyrido[3,2-d]pyrimidin-4-ylamine (27 mg, LC/MS m/z=165 [M+H]+) as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; at 40℃; under 10032.9 Torr; for 20h; | The bromomethylketone prepared as described in Steps A-C of the synthesis of Intermediate 10 (2.02 g, 6.60 mmol) was combined with FORMAMIDINE acetate (1.37 g, 13.2 mmol) in-130 mL of NH3 (1) and heated in an autoclave at 40 °C and 194 psi for 20 h. The NH3 was allowed to evaporate, the residue was dissolved in DCM and filtered. The filtrate was concentrated. Purification by flash chromatography (silica, 10percent of 1: 9 NH4OH/METHANOL in DCM) afforded 649 mg of the imidazole product. APOS;H NMR (400 MHz, CD30D) : 8 7.56 (d, J = 1.2 Hz, 1H), 6.74 (d, J = 1. 2 Hz, 1H), 4.13 (br s, 2H), 2.82 (m, 2H), 2.74 (m, 1H), 1.97 (m, 2H), 1.54 (m, 2H), 1.44 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.63% | In ISOPROPYLAMIDE; at 150℃; for 12h; | A mixture of 3-amino-isonicotinic acid (32)(26.24 g, 190.0 mmol) and formamidine acetate (39.56 g, 380 mmol) in dimethylacetamide (100 ml) was stirred and heated to 150° C. The reaction was maintained at this temperature with stirring for 12 hours before it was allowed to cool to 25° C. and then basified with sodium bicarbonate solution (5percent aqueous) until pH 7-8 was attained. The resultant pale brown solid was removed by filtration, washed with water (20 ml) and dried in a desiccator to give the desired compound (24.50 g, 87.63percent) which required no further purification. m/z (LC-MS, ESP): 148 [M+H]+, R/T=1.09 mins. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61.4% | 6-Benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one A mixture of ethyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (50.0 g, 0.168 mol), formamidine acetate (16.2 g, 0.201 mol), 4.37 M of sodium methoxide in methanol (190 mL) and methanol (200 mL, 5 mol) was heated to 85 C. for 16 hour in a 350 ml sealed reaction vessel. The mixture was allowed to cool and reduced in vacuo. The residue was dissolved in 1N NaOH (150 ml) and poured over ice. Glacial acetic acid was added to the mixture until the pH of the mixture was 7 and a tan solid precipitated out. the solid was filtered, washed with water and cold ether, and dried on high vacuum to yield the title compound as a tan solid. (26.2 g, 61.4%). MS: M+H=242.2. 1H NMR (DMSO-d6): delta 2.29 (t, 5.8 Hz, 2H); 2.61 (t, 5.8 Hz, 2H); 3.26 (s, 2H); 3.64 (s, 2H); 7.21-7.36 (m, 6H); 7.96 (s, 1H). | |
61.4% | Intermediate 16-Benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one A mixture of ethyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (50.0 g, 0.168 mol), formamidine acetate (16.2 g, 0.201 mol), 4.37 M of sodium methoxide in methanol (190 mL) and methanol (200 mL) was heated at 85 C. for 16 hour in a 350 mL sealed reaction vessel. The mixture was allowed to cool and concentrated in vacuo. The residue was dissolved in 1N NaOH (150 mL) and poured over ice. Glacial acetic acid was added to the mixture until the pH of the mixture was 7 and a tan solid precipitated out. The solid was filtered, washed with water and cold ether, and dried on high vacuum to yield the title compound as a tan solid (26.2 g, 61.4%).LC-MS: 242.2 [M+1]+; 1H NMR (400 MHz, DMSO-d6): delta 2.29 (t, 2H, J=5.8 Hz), 2.61 (t, 2H, J=5.8 Hz), 3.26 (s, 2H), 3.64 (s, 2H), 7.21-7.36 (m, 6H), 7.96 (s, 1H). | |
61.4% | INTERMEDIATE 1 6-Benzyl-5,6,7,8-tetrahydropyrido [4,3-d] pyrimidin-4(3H)-one[00273] A mixture of ethyl l-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (50.0 g,0.168 mol), formamidine acetate (16.2 g, 0.201 mol), 4.37 M of sodium methoxide in methanol (190 mL) and methanol (200 mL) was heated at 85 0C for 16 hour in a 350 mL sealed reaction vessel. The mixture was allowed to cool and concentrated in vacuo. The residue was dissolved in IN NaOH (150 mL) and poured over ice. Glacial acetic acid was added to the mixture until the pH of the mixture was 7 and a tan solid precipitated out. The solid was filtered, washed with water and cold ether, and dried on high vacuum to yield the title compound as a tan solid (26.2 g, 61.4 %).MS: 242.2 [M+l]+; 1H NMR (400 MHz, DMSO-d6): 2.29 (t, 2H, J = 5.8 Hz), 2.61 (t, 2H, J = 5.8 Hz), 3.26 (s, 2H), 3.64 (s, 2H), 7.21-7.36 (m, 6H), 7.96 (s, IH). |
55% | With sodium methylate; In methanol; at 70℃; for 18.0h; | To a solution of ethyl l-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (1.0 g, 3.4 mmol) and formamidine acetate (0.420 g, 4.03 mmol) in MeOH (6.7 mL) was added NaOMe in MeOH (4.6 ml, 20 mmol) and the resulting suspension was stirred at 70 C for 18 h. The mixture was cooled to RT and concentrated under reduced pressure. The residue was partitioned between water (1 mL) and 3: 1 CHCh:iPrOH (3 mL). The layers were separated and the organic layer was washed with brine (1 mL), dried over Na2S04 and concentrated under reduced pressure to afford the title compound (444 mg, 55%) as a light yellow solid.MS (ES+) C14H15N3O requires: 241, found: 242 [M+H]+. |
With sodium alcoholate; In ethanol; for 2.0h;Reflux; | Step A:l-Benzyl-3-ethoxycarbonyl-4-piperidone hydrochloride (12.89 g, 43.3 mmol) was suspended in a sodium methoxide solution in methanol (25 % wt/wt, 50 mL, 216. 2 mmol) and formamidine acetate (5.4 g, 51.9 mmol) was added to the mixture. The reaction mixture was refluxed until all of the starting material was consumed (2 h). The methanol was removed under reduced pressure, and the resulting white solid was dissolved in a 3/1 mixture of chloroform / isopropanol. The mixture was washed with water and brine, dried over Na2S04, filtered and evaporated to give the desired product as a white solid (9.4 g). MS (ESEI): 242.1 [M+l]+ | |
With sodium alcoholate; In water; for 2.0h;Reflux; | l-Ben2yl-3-ethoxycarbonyl-4-piperidone hydrochloride (12.89 g, 43.3 mmol) was suspended in a sodium methoxide solution in methanol (25 % wt wt, 50 mL, 216. 2 mmol) and formamidine acetate (5.4 g, 51.9 mmol) was added to the mixture. The reaction mixture was refluxed until all of the starting material was consumed (2 h). The methanol was removed under reduced pressure, and the resulting white solid was dissolved in a 3/1 mixture of chloroform / isopropanol. The mixture was washed with water and brine, dried over Na2SC>4, filtered and evaporated to give the desired product as a white solid (9.4 g). MS (ESEI): 242.1 [M+l]? |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; for 6h;Reflux; | Example 10: Preparation of 7-methoxy-6-(3-morpholin-4-ylpropoxy)-3/f-quinazolin-4-one; 4-Methoxy-5-(3-mophiholin-4-ylpropoxy)-2-nitrobenzoic acid ethyl ester (50g) was hydrogenated using 10percent palladium on carbon (50percent wet, 5g) in methanol (250ml) at" 3.0-3.5 kg/cm2 for 3 hours. After completion of reaction, catalyst was removed by filtration. Formamidine acetate (22g) in methanol was added to resulting filtrate and refluxed for 6 hours. After completion of reaction, the reaction mass was cooled to room temperature, stirred for 2 hours. The resulting product was filtered, washed with methanol (50 ml) and dried to betaive 33g (73percent) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In ethanol; for 24.0h;Heating / reflux; | 6-bromo-7-methoxyquinazoline-4(3H)-one <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (type T) (5.63 g, 23 mmol) was dissolved in EtOH (100 mL), formamidine acetate (4.76 g, 46 mmol) added and refluxed for 1 d. Water (200 mL) was then added, the precipitated product filtered out and washed with 70% ethanol. (Yield: 4.14 g, 71%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7H-Pyrrolo[2,3-d]pyrimidin-4-ol (7).; Formamidine acetate (5, 1.04 Kg,10 mol, 1.25 equiv) was added to 7.52 L of (21percent wt) sodium ethoxide (EtONa) in ethanol (EtOH, 62.5 equiv) and the resulting solution was stirred for 60 minutes. <strong>[52133-67-2]2-cyano-4,4-diethoxy-butyric acid ethyl ester</strong> (4, 1.8 Kg, 8.0 mol) was then added and the resulting reaction mixture was refluxed for seven hours. The stirring was turned off after the solution was cooled and the solids were allowed to settle. The supernatant ethanol solution was removed, leaving the solids in the bottom of the reaction flask. The ethanol was evaporated and the residue was added back to the solids remaining in the reaction flask with water and ice at a ratio of 600 mL/mol. A solution of 6 N aqueous HCl was added to the resulting solution at a ratio of 500 mL/mol at 15° C. The resulting solution was then heated at 45° C. for 45 minutes. The solution was again cooled to 15° C. and the pH was adjusted to 8.0 with the addition of aqueous ammonium hydroxide. The precipitated solids were collected by filtration, washed with water (2.x.225 mL/mol) and pulled dry. The solids were further washed with 1:1 ethyl acetate/heptane (500 mL/mol), then heptane (2.x.250 mL/mol) and dried in vacuum to afford 7H-pyrrolo[2,3-d]pyrimidin-4-ol (7, 738.6g, 1081 g theoretical, 68.3percent) as yellow to brown to yellow crystalline material. For 7: 1H NMR (DMSO-d6, 300 MHz) delta ppm 11.88 (bs, 1H), 11.80 (bs, 1H), 7.81 (s,1H), 7.02 (dd,1H, J=3.2, 2.3 Hz), 6.42 (dd, 1H, J=3.5, 2.3 Hz); C6H5N3O (MW, 135.12), LCMS (EI) m/e 136 (M++H) and (M++Na) m/e 158. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.7% | In 1,2-dimethoxyethane; at 110℃; for 15h; | The compound 2-bromo-1-cyclopropylethanone (12.0 g, 74.1 mmol) and formamidine acetate (23.1 g, 222.3 mmol) were dissolved in 100 mL of ethylene glycol and reacted at 110 C for 15 hours. After the reaction was completed, 500 mL of water was added, and the mixture was washed three times with dichloromethane (500 mL×3), then the aqueous phase was adjusted to pH 8 with a 1 M aqueous NaOH solution, and the aqueous phase was extracted twice with dichloromethane (500 mL×2), organic phase was dried and concentrated to give the desired product 7.5g, yield 93.7%. |
In ethylene glycol; at 135℃; | A mixture of 2-bromo-l-cyclopropylethanone (1.63 g, 10.0 mmol) and formimidamide acetate (5.24 g, 50.0 mmol) in ethylene glycol (50 mL) was heated at 135deg;C overnight. After cooling, the mixture was diluted with water (50 mL), and extracted several times with ether. The combined organic layers were dried over MgSO4, filtered, and concentrated to afford the crude product which was directly used in next step reaction without further purification. LCMS: (M+H)+= 109.3. | |
With ammonia; at -78 - 20℃;Sealed tube; | A. Preparation of 4-cyclopropyl-1H-imidazole Ammonia (~75 mL) was condensed into a pressure vessel containing formamidine acetate (60 g, 0.58 mol) and a stir bar at -78 C. 2-bromo-1-cyclopropyl-ethanone (10.2 g, 0.063 mol) was added dropwise and the pressure vessel was sealed and warmed to room temperature and stirred for 12 hours. The reaction mixture was then cooled to -78 C. before being carefully opened. The cooling bath was removed and the ammonia was allowed to evaporate. The residue was dissolved in 100 mL of water and 20 mL saturated sodium bicarbonate solution, and then solid sodium chloride was added until the solution was saturated. This mixture was extracted with ethyl acetate (4*100 mL) and the organic phase was dried with sodium sulfate before being evaporated to yield 4-cyclopropyl-1H-imidazole as a yellow oil (70-80% purity, 5.3 g, 78% yield, M+1=109.1) which was used without further purification. Reverse-phase HPLC (0.1% HCl H2O, MeCN) of the crude compound gave an analytically pure sample (1.0 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In formamide; at 160℃; for 6.0h;Inert atmosphere; | General procedure: A mixture of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (2.6 g, 11.54 mmol) and formamidine acetate (1.20 g, 11.54 mmol) in formamide (4 mL) was heated to 160 oC for 6 h. Within this time period at every 2 h additional formamidine acetate (1.20 g, 11.54 mmol) was added. Water (30 mL) was added and the precipitate that resulted was filtered off, washed with water, and dried in a vacuum oven to give the pyrimidine as a tanned solid (2.3 g, 96%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Zn(OTf)2, 0.27g (2.5 mmol) of formamidine acetate, 58mg (0.25 mmol) nitrile ,0.20 mL DMF, and 0.40 mL (12.5 mmol) of anhydrous hydrazine was added. The vessel was sealed and the mixture was stirred in an oil bath at 30C for 36 hours. The reaction solution was cooled to room temperature and the seal was removed. Sodium nitrite (5.0 mmol, 345 mg) in 5 mL of water was slowly added to the solution and followed by slow addition of 1M HCl during which the solution turned bright red in color and gas evolved. Addition of 1M HCl continued until gas evolution ceased and the pH value is 3. (Caution: this step generates a large amount of toxic nitrogen oxide gasses and should be performed in a well ventilated fume hood). The mixture was extracted with EtOAc and the organic phase dried over sodium sulfate. The EtOAc was removed using rotary evaporation and the residue purified using silica column chromatography (Hexane:EtOAc=7: l) to give 50mg product as red solid, the yield is 70%. 1H NMR (500 MHz, CDC13) delta 1.49 (9H, s), 4.45 (2H, d, J = 5 Hz ), 4.97 (1H, bs), 7.53 (2H, d, J = 10 Hz), 8.60 (2H, d, J = 10 Hz), 10.21 (1H, s); 13C MR (125 MHz, CDC13) delta 39.07, 51.82, 118.84, 119.19, 120.76, 132.11, 141.12, 142.56, 149.36; HRMS [M+Na]+ m/z calcd. for [C9H16N502]+ 310.1276, found 310.1274. | |
62% | Synthesis of SiR-Tz (FIG. 8) (0148) 4-Cyanobenzylamine HCl was Boc-protected with Boc-anhydride. The Boc-protected amine was converted to the tetrazine 8 (Yang, et al., 2012, Angew. Chem., Int. Ed. 51:5222-5225). The Boc-group of tetrazine 8 was removed by treating the compound with a 1:1 mixture of TFA and dichloromethane and immediately coupled with SiR-OH (Lukinavicius, et al., 2013, Nature Chem. 5:132-139) mediated by TBTU and iPr2NEt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In 2-methoxy-ethanol; at 130℃; for 18h; | A mixture of 2-amino-4-nitrobenzoic acid (10.0 g, 54.93 mmol) was refluxed at 130 C. for 18 h in methoxyethanol (50 mL) and formamidine acetate (11.43 g, 109.81 mmol). The clear reaction mixture was cooled to room-temperature to form a yellowish precipitant. The solvent was removed under vacuum, and the precipitant was washed several times with aqueous ammonia (0.01 M). The solid was dried in vacuo to yield 8.9 g (84%) of a light yellow powder. 1H NMR Data: dmso-d6-ppm (delta); 12.68 (1H), 8.37 (d, 1H), 8.33 (d, 1H), 8.26 (1H) and 8.23 (dd, 1H). |
In ethanol;Reflux; | The 46g (0 · 25mol) 2- amino-4-nitrobenzoic acid and 52g (0 · 5mol) was added formamidine acetate 500mL single-necked round bottom flask was added 200mL ethanol, refluxed 4~6h,The system will have a lot of yellow precipitate. At this point heating was stopped and the system was cooled to about 50 C, part of the ethanol was removed in vacuo to approximately system 50mL, added to the system 30mL, stirred for several minutes after the refrigeration system LH, filtered, the filter cake was washed successively with chilled ethanol (3 X 1o mL) washed with water (2 X 10 mL) and dried under vacuum to obtain the 7-nitro - -quinazolinone 2, khaki-colored crystalline solid 39.6g, yield: 82.8%, m.rho: 282~284 C, IR (KBr) v: 3174,3064,2960,1683,1613,1528,803; this compound was used without further purification was used directly in the next step chlorine substitution reactions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With ethanol; sodium ethanolate;Reflux; | Preparation 16-Benz i-5,6,7,8-tetrah dropyrido[4,3-rf]pyrimidin-4 3H)-Sodium methylate (43 g, 0.8 mol) was added to a mixture of imidoformamide acetate (39.85 g, 0.383 mol) and ethyl l-benzyl-4-oxopiperidine-3-carboxylate (110 g, 0.37 mol) in absolute ethanol (250 mL). The reaction mixture was refluxed for 3-4 h, during which time the course of the reaction was monitored by TLC (Merck UV-254; chloroform/methanol 4:1 ). The mixture was then filtered, and the filtrate was evaporated. Water (-400 mL) was added to the residue, and the obtained aqueous solution was acidified to pH 7-8. The product was then extracted with chloroform, and the extract was dried over MgS04 and evaporated to give the title compound in 55% (50.7 g) yield. The product was then recrystallized from ethylacetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.4 g | In ethyl acetate; for 12.0h;Reflux; | A mixture of iron powder (29 g, 0.527 mol) and acetic acid 270 mL was stirred and heated to 50-60C till a grey white suspension was formed. The suspension was diluted with 150 mL methanol. Methyl 4-methoxy-3-benzyloxy-6-nitrobenzoate 7 (50g, 0.1575 mol) was added portion wise at regular intervals. The reaction was maintained at the same temperature for 5-6 hr. The mixture was filtered hot and the filtrate was evaporated to a residue mass under reduced pressure. The residue was extracted with ethyl acetate 2 × 300 mL. The combined organic layers were washed with water* and formamidine acetate 28.6 g (0.2747 mol) was added to the organic layer and refluxed for 12 hr. Reaction mass was cooled to 25-30C and stirred for 1 hr and precipitated solid was collected by filtration. Isolated solid was slurry washed with 250 mL methanol and dried to get the off white powder 9, 38.4 g (yield 91%, purity 98%); m.p. 258-60C; 1HNMR (DMSO-d6, 300 MHz): 12.076 (s, 1H), 7.986 (s, 1H), 7.342-7.545 (m, 6H), 7.152 (s, 1H), 5.206 (s, 2H), 3.913 (s, 3H); MS (EI): m/z 283 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In ethanol; at 160℃; for 0.5h;Microwave irradiation; | A Biotage microwave vial was charged with 3-aminoisonicotinic acid (691 mg, 5.0 mmol), formamidine acetate (573 mg, 5.5 mmol), and ethanol (10 mL). The reaction mixture was heated in the microwave at 160 °C for 30 min, diluted with H20 (20 mL), and cooled to 0 °C. The suspension was filtered and the solids were washed with cold H20 (10 mL) to provide quinazoline A2 (259 mg, 35percent) as a white solid: LC-MS (>98percent) m/z = 148.0[M+H], Rt= 0.604. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.858 g | In ethanol; for 24.0h;Reflux; | A mixture of <strong>[169045-04-9]2-amino-5-bromo-4-methoxybenzoic acid</strong> (1 .25 g, 3.6 mmol) and formimidamide acetate (0.75 g, 7.2 mmol) in EtOH (15 mL) was refluxed for 24 h. The mixture was cooled to room temperature and the solid was filtered, washed with water, and dried to provide 6- bromo-7-methoxyquinazolin-4(1 H)-one as a white solid (0.858 g). MS (M+1 ) = 255.0/257.0. 1H NMR (DMSO-d6) delta 12.30 (br. s, 1 H), 8.21 (s, 1 H), 8.12 (s, 1 H), 7.25 (s, 1 H), 4.00 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In ethanol; for 16h;Reflux; | To a solution of <strong>[150812-32-1]2-amino-4-bromo-5-chlorobenzoic acid</strong> (500 mg,2mmol) in EtOH (20 mL) at RT, formamidine acetate (620 mg, 6 mmol) was added. The mixture was reflux for 16 hour. The mixture was concentrated in vacuo, and the residue was washed by saturated NaHCO3 aqueous solution, and a mixture of ethylacetate/petroleum ether = 1:2. The solid was dried in vacuo to get the product (520 mg, 100% yield) which was used directly in next step without further purification. ESI-MSm/z: 259.0 [M+H]. |
In ethanol; for 16h;Reflux; | 7-Bromo-6-chloroquinazolin-4-ol To a solution of <strong>[150812-32-1]2-amino-4-bromo-5-chlorobenzoic acid</strong> (500 mg, 2mmol) in EtOH (20 mL) at RT, formamidine acetate (620 mg, 6 mmol) was added. The mixture was reflux for 16 hour. The mixture was concentrated in vacuo, and the residue was washed by saturated NaHCO3 aqueous solution, and a mixture of ethyl acetate/petroleum ether = 1:2. The solid was dried in vacuo to get the product (520 mg, 100% yield) which was used directly in next step without further purification. ESI-MS m/z: 259.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | The preparation of 4-hydroxyl-5-chloro-6-methylpyrimidine ;8.80g (0.16mol) of CH3ONa in methanol was added slowly to a solution of 11.30g (0.11mol of formimidamide in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 hrs after addition at room temperature. ;Followed by addition of 11.17g ( 0.068mol ) of ethyl 2-chloro-3-oxobutanoate, the mixture was continued stirring for another 5-7 hrs at room temperature. ;After the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HCl, and then filtered to afford orange-yellow soilid, the water phase was extracted with ethyl acetate (3x50mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. ;The residue was dissolved to 50ml of ethyl acetate, stand overnight to obtain 6.48g as orange-yellow soilid with yield of 66%. m.p. 181~184C. | |
66% | 1) Preparation of 4-hydroxy-5-chloro-6-methylpyrimidineStirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide methanol solution was dropwise completed stirring was continued at room temperature 2h. To the above solution was then added dropwise 11.17g (0.068mol) of 2-chloroacetyl ethyl acetate, the reaction was stirred for 5-7 hours at room temperature continued, monitored by TLC after completion of the reaction, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid 1-6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and desolvation. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 . | |
66% | With stirring at room temperature, to 11.30g (0.11mol) of formamidine acetate in 50ml of methanol was slowly added dropwise 8.80g (0.16mol) of methanol solution of sodium methoxide, after dropwise addition, at room temperature and stirring was continued for 2h. To the above solution was then added dropwise 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate, continued stirring for 5-7 hours at room temperature. After completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, adjusted with hydrochloric acid pH = 5 ~ 6, orange solid was suction filtered, the aqueous phase was extracted with ethyl acetate (3 × 50ml), dried over anhydrous magnesium sulfate, filtered, removing solvent. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66%, m.p. 181 ~ 184 deg. C. |
66% | Stirring at room temperature to a solution of methanol 50ml 11.30g (0.11mol) of formamidine acetate was added slowly dropwise 8.80g (0.16mol) of sodium methoxide in methanol, stirring was continued at room temperature completion of dropwise 2h. Then added dropwise 11.17g (0.068mol) ethyl 2-chloroacetoacetate intermediate to the above solution, the reaction was stirred for 5-7 hours at room temperature continued. After completion of the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, adjusted to pH = 5 with hydrochloric acid to 6, orange solid was suction filtered, the aqueous phase with (3 × 50ml) and extracted with ethyl acetate, dried over anhydrous magnesium sulfate, filtered off solution. The residue was dissolved in 50ml of ethyl acetate and allowed to stand overnight, and filtered to give an orange solid 6.48g. Yield 66% | |
66% | To a solution of 11.30 g (0.11 mol) methylhydrazine acetate in 50 ml of methanol was slowly added dropwise 8.80 g with stirring at room temperature.(0.16 mol) of sodium methoxide in methanol, and the mixture was stirred at room temperature for 2 h. Then 11.17 g (0.068 mol) was added dropwise to the above solution.Ethyl 2-chloro-acetoacetate was stirred at room temperature for 5-7 hours. After TLC monitoring was completed, the solvent was distilled off under reduced pressure and salt was used.The pH was adjusted to 5-6, and the orange solid was filtered by suction. The aqueous phase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, and dissolved.The combined product was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48 g of an orange-yellow solid. Yield 66.0% | |
66% | A solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise to a solution of 11.30 g (0.11 mol) of methylacetoacetate in 50 ml of methanol at room temperature with stirring, and the mixturewas stirred at room temperature for 2 hours. Then, 11.17 g (0.068 mol) of the intermediate 2-chloroacetoacetic acid ethylacetate was added dropwise to theabove solution, and the reaction was continued for 5-7 hours while stirring at room temperature. After the TLCmonitoring reaction was completed, the solvent was evaporated under reduced pressure, and the pH wasadjusted to 5-6 with hydrochloric acid. The orange solid was collected by suction filtration, and the aqueousphase was extracted with ethyl acetate (3×50 ml), dried over anhydrous magnesium sulfate, filtered and shaken.Dissolved. The residue was dissolved in 50 ml of ethyl acetate, allowed to stand overnight and filtered to give 6.48g of an orange-yellow solid. The yield of 66%. | |
66% | 10343] A solution of 8.80 g (0.16 mol) of CH3ONa in methanol was added slowly to a solution of 11.30 g (0.11 mol) of formimidamideacetate in 50 mL of methanol at room temperature under stirring, the mixture was stirred for another 2 h after addition at room temperature. Followed by addition of 11.17 g (0.068 mol) of ethyl 2-chloro-3-oxobu- tanoate, the mixture was continued stirring for another 5-7 h at room temperature. Afier the reaction was over by Thin-Layer Chromatography monitoring, the reaction mixture was concentrated under reduced pressure and pH was adjusted to 5-6 with HC1, and then filtered to afford orangeyellow solid, the water phase was extracted with ethyl acetate (3x50 mL), dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was dissolved to 50 ml of ethyl acetate, stand overnight to obtain 6.48 g as orange-yellow solid with yield of 66%. m.p. 181-184 C. | |
66% | To a solution of 11.30 g (0.11 mol) of formamidine acetate in 50 ml of methanol, a solution of 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise with stirring at room temperature.Stirring was continued for 2 h at room temperature.Then, 11.17 g (0.068 mol) of an intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was further stirred at room temperature for 5-7 hours.After the TLC monitoring reaction was completed, the solvent was evaporated under reduced pressure, and the mixture was adjusted to pH 5 to 6 with hydrochloric acid, and filtered to give an orange-yellow solid.The aqueous phase was extracted with (3 × 50ml) of ethyl acetate, dried over anhydrous magnesium sulfate, filtered, desolventized.The residue was dissolved in 50ml of ethyl acetate, allowed to stand overnight, and filtered to give an orange-yellow solid 6.48g. Yield 66%, | |
66% | To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h.Then, 11.17 g (0.068 mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was continued to be stirred at room temperature for 5-7 hours.After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5-6 with hydrochloric acid.Filtration with suction yielded an orange-yellow solid, and the aqueous phase was extracted with (3 × 50 ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated.The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. The yield is 66%, | |
66% | To a solution of 11.30 g (0.11 mol) formamidine acetate in 50 ml of methanol under stirring at room temperature, 8.80 g (0.16 mol) of sodium methoxide in methanol was slowly added dropwise, and stirring was continued at room temperature for 2 h. Then, 11.17g (0.068mol) of intermediate ethyl 2-chloroacetoacetate was added dropwise to the above solution, and the reaction was stirred at room temperature for 5-7 hours. After the reaction was monitored by TLC, the solvent was distilled off under reduced pressure, and the pH was adjusted to 5 with hydrochloric acid. 6, suction filtration to obtain orange-yellow solid, the aqueous phase was extracted with (3 × 50ml) ethyl acetate, dried over anhydrous magnesium sulfate, filtered and desolvated. The residue was dissolved in 50 ml of ethyl acetate, left overnight, and filtered to obtain 6.48 g of orange solid. 66% yield | |
With sodium methylate; In methanol; at 5 - 20℃; | General procedure: A solution of formamidine acetate (0.70 mol) in methanol (150 mL)was stirred at 5-10 C, and then CH3ONa (1.20 mol) in methanol(150 mL) newly prepared was added slowly under stirring, followed byaddition of M-1 (0.50 mol) in methanol (100 mL). The mixture wascontinued stirring for another 3-4 h at room temperature and thenconcentrated under reduced pressure. The residue was adjusted to pH5-6 with diluted HCl, the precipitated solid was filtered to afford M-2 asa white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | General procedure: A solution of sodium ethoxide in ethanol was cooled to0 C under argon atmosphere. Diethyl 2-formylsuccinatewas added under stirring. After 5 min, the correspondingamidine was added at 0 C and stirring was continued at rtfor 3 days. Aqueous hydrogen chloride solution (5 %) wasadded and it was stirred for 30 min. After addition of waterthe ethanol was removed in vacuo at 30 C. The precipitatewas filtered off to give compound 1 (X = H, Me, Ph, SMe;Y = H, R1 = Et) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With sodium methylate; In methanol; at 70℃; for 3h; | Compound 40 (2 g, 7.77 mmol) in methanol (10 mL) formimidamide acetate (4.05 g, 38.9 mmol) and 1 mol / L sodium methoxide methanol solution (11.7 mL, 11.7 mmol) were added, and the mixture was stirred at 70 ° C. for 3 hours. 1 mol / L hydrochloric acid aqueous solution was added to the reaction solution, extracted four times with ethyl acetate.The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained residue was purified by silica gel chromatography (chloroform / methanol) to obtain Compound 41 (620 mg, yield: 34percent) |
680 mg | The Preparation of Compound 14E: MeONa (2.6 g, 48.58 mmol) was dissolved in MeOH (50 mL). The reaction mixture was cooled to 5° C., and formamidine acetate (3.0 g, 29.15 mmol) was added. The reaction mixture was stirred for 0.5 hour, and then compound 14D (5.0 g, 19.43 mmol) was added. The reaction mixture was stirred to reflux overnight. The reaction was monitored via TLC (DCM/Methanol=10:1). After the reaction was completed, the reaction mixture was cooled to room temperature, evaporated to remove most of the solvent. The residue was extracted with EA. The organic phase was washed with brine, dried with anhydrous Na2SO4 and concentrated, to obtain a crude product. The crude product was purified by silica gel chromatography to obtain a purified compound 14E (680 mg, yield: 14.7percent) as a light yellow solid. | |
680 mg | MeONa (2.6 g, 48.58 mmol) was dissolved in MeOH (50 mL). The reaction mixture was cooled to 5° C., and formamidine acetate (3.0 g, 29.15 mmol) was added. The reaction mixture was stirred for 0.5 hour, and then compound 14D (5.0 g, 19.43 mmol) was added. The reaction mixture was stirred to reflux overnight. The reaction was monitored via TLC (DCM/Methanol=10:1). After the reaction was completed, the reaction mixture was cooled to room temperature, evaporated to remove most of the solvent. The residue was extracted with EA. The organic phase was washed with brine, dried with anhydrous Na2SO4 and concentrated, to obtain a crude product. The crude product was purified by silica gel chromatography to obtain a purified compound 14E (680 mg, yield: 14.7percent) as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 85℃; for 16h; | Step-3: (0915) Preparation of imidazo[5,1-f][1,2,4]triazin-4(3H)-one: (0916) [00347] To a solution of <strong>[1179361-84-2]ethyl 1-amino-1H-imidazole-5-carboxylate</strong> (0.38 g, 2.44 mmol) in ethanol (20 mL) was added formamidine acetate (1.27 g, 12.25 mmol) and the reaction mixture was heated at 85 C for 16 h. After completion of the reaction, the reaction mixture was cooled to room temperature and the solid obtained was filtered, washed with hexane and dried under high vacuum to afford the title compound imidazo[5,1-f][1,2,4]triazin-4(3H)-one (0.17 g, crude) as a off-white solid. Calculated (M+H): 137.04; Found (M+H): 137.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | at 180℃; for 3h; | 2-Amino-3-methylbenzoic acid (125 g, 0.820 mol), formamidine acetate (257 g, 2.46 mol) and formamide (32.5 mL, 0.8200 mol) wereminxed in a 2L R.B fitted with Mechanical stirrer. The reactionminxture was heated at 180 C for 3h. The reaction completion was monitored by LCMS. After completion, the reactionminxture was cooled to RT and diluted with 2N NaOH solution (300 mL). After stirring at the same temperature for 15 min, the reactionminxture neutralized with 1 .5N HC1 solution. The solid precipitated was filtered off, washed with ice cold water and dried under vacuum to yield 8-methyl-3H-quinazolin-4-one (125 g, 94%) as an off white solid. 1H NMR (400 MHz, DMSO-d6, ppm) 12.2 (bs, 1H), 8.1 (s, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.7 (d, J = 7.2 Hz, 1H), 7.4 (t, J = 7.6 Hz, 1H), 2.5 (s, 3H); LC/MS(ESI)161 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.4% | In neat (no solvent); at 160℃; for 0.5h; | The mixture of <strong>[58483-95-7]5-amino-2-chloroisonicotinic acid</strong> (5.00g, 29.07mmol) and formamidine acetate (6.00g, 58.14mmol) was stirred at 160°C for 0.5h, cooled, water (100mL) was added. The mixture was refluxed under vigorous stirring for 20min, cooled again. The precipitate formed was collected, washed with water and dried to give 4.74g intermediate 15 as off-white power. Yield 90.4percent. mp>320°C. MS m/z (ESI) 182.4 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2-methoxy-ethanol; at 120℃; for 3.0h;Inert atmosphere; | Compound 1A (5.9 g, 18.94 mmol) and formamidine acetate (3.55 g, 34.10 mmol) were dissolved in ethylene glycol monomethyl ether (10 mL), and the reaction mixture was stirred under nitrogen protection at 120 C for 3 hours. TLC showed that the reaction was complete. The reaction solution was cooled down to room temperature, the solids were precipitated and filtered, and the filter cake was washed with EA (10 mL x 2), PE (20 mL x 3) and water (50 mL x 2), respectively. Compound 1B was obtained after drying. LCMS (ESI) (5-95AB): m/z: 254.9 [M+1]. |
Tags: Formimidamide acetate | Inorganic Salts | Amines | Aliphatic Chain Hydrocarbons | Synthetic Reagents | Organic Building Blocks | 3473-63-0
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :
Total Compounds: mg
The concentration of the dissolution solution you need to prepare is mg/mL