Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 57489-77-7 | MDL No. : | MFCD08273918 |
Formula : | C6H3Cl2N3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JMTFWCYVZOFHLR-UHFFFAOYSA-N |
M.W : | 188.01 | Pubchem ID : | 11074154 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 9 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 43.01 |
TPSA : | 30.19 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.85 cm/s |
Log Po/w (iLOGP) : | 1.73 |
Log Po/w (XLOGP3) : | 2.25 |
Log Po/w (WLOGP) : | 2.04 |
Log Po/w (MLOGP) : | 1.78 |
Log Po/w (SILICOS-IT) : | 1.77 |
Consensus Log Po/w : | 1.91 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.03 |
Solubility : | 0.176 mg/ml ; 0.000936 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.52 |
Solubility : | 0.568 mg/ml ; 0.00302 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.95 |
Solubility : | 0.212 mg/ml ; 0.00113 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.89 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-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 |
---|---|---|
86% | at 20 - 60℃; for 16 h; Inert atmosphere | POC13 (130 mL) was added to pyrazolo[1,5-a]pyrimidine-5,7-diol (10g. 66 rnrnol). The suspension was cooJed to 0 °C ard N,N-dimethylaniline (23 mL. 179 mmoi) was siowy added. After warming to room temperature, the reaction was heated at 60 °C under N2 for 16 hr. Upon coohng, the reactior mixture was concentrated in aeuo to give a brown viscous liquid, which was slowly poured onto ice and aIowed to warm to room temperature. The pH was adjustedpH 8 with saturated NaHCO3. The organic layer was then extracted with CH2C12 (4 x 50 mL), dried (MgSO4), and concentrated in vacuo to give a brown ‘iquid. Purification by flash column chromatography using 1:1 v/v DCM:hexanes to 2:1 v/v DCM:hexanes afforded the title compound (10.7 g, 86percent yield) as a white crystalline solid. MS m/z 189.36 [M+1]. |
64% | at 0 - 60℃; for 16 h; Inert atmosphere | Step B - Synthesis of 5,7-dichloropyrazolo[ l,5-a]pyrimidine (lnt-9b)lnt-9a Int-ψbTo pyrazolo[l,5-aJpyrimidine-5,7-diol (Int-9a, 9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 ( 125 mL, 1341.1 mmol). The flask was then cooled to 0 0C and OC2009.701887N, N-dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction mixture was then heated at 60 0C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHCψ3 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na?Sψ4) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50percent CHbCb/hexanes (to elute aniline) followed by 75percent CHaC^/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5-a]pyrimidine (Int-9b) as a white solid (7.7 g, 40.8 mmol, 64percent). |
64% | Stage #1: at 0 - 60℃; for 16 h; Inert atmosphere |
To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0°C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60°C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na2S04) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50percent CHaCLVhexanes (to elute aniline) followed by 75percent CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5~ a]pyrimidine as a white solid (7.7 g, 40.8 mmol, 64percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium hydroxide In water at 90℃; for 0.5 h; | 1 g of 5,7-dichloropyrazolo [2,5-a] pyrimidine was suspended in 25 mL of 1N aqueous sodium hydroxide solution and heated to 90 ° C,Stir for 0.5 h. The reaction was detected by thin layer chromatography, and after completion of the reaction, the reaction solution was cooled to room temperature.The solution was adjusted to pH = 2 with 1N HCl solution to give a suspension,5-chloropyrazolo [1,5-a] pyridine-7 (4H) -one (0.9 g, yield = 99percent) was obtained by standing filtration. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-Bromosuccinimide; ammonium cerium(IV) nitrate In acetonitrile for 1 h; Heating / reflux | To a solution of 5, 7-CHLOROPYRAZOLO [1, 5-A] PYRIMIDINE (1 g, 5.32 MMOL) in ACETONITRILE (20 CM3) was added N-BROMOSUCCINIMIDE (1.04 g, 5. 85 MMOL) and ceric ammoinum nitrate (0.029 g, 0.053 MMOL). The reaction was heated at reflux for 1 hour. The reaction was washed with aqueous sodium metabisulfite (30 CM3, 10percent solution) and then brine (20 cm3). The organic fraction was dried with magnesium sulphate and CONCENLRATED IN VACUO. The product was purified on silica ELUTING with 20percent ETHYLACETAT in hexane, to yield the title compound as A yellow solid (1. 33 g, 92percent). δH (400 MHz; d4-CDCl3) 8.22 (1H, s), 7.04 (1H, s). |
89% | With N-Bromosuccinimide In acetonitrile at 20℃; for 2 h; | To a solution 5,7-dichloropyrazolo[l ,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (3 13.5 g, 89percent) as light yellow solid. NMR (300 MHz, CDCl3): 5 7.04 (s, 1 H), 8.21 (s, 1 H); MS ESI [M + H]+265.9, calcd for [C6H2BrCl2N3+H]+265.9. |
89% | With N-Bromosuccinimide In acetonitrile at 20℃; for 2 h; Inert atmosphere | To a stirred solution of sodium ethoxide in EtOH, which was prepared from sodium (281.3 g, 12.0 mol) and EtOH (10 L) by the conventional method, were added diethyl malonate (963.7 g, 6.02 mol) at ambient temperature and then compound lH-pyrazol-3-amine (500 g, 6.02 mol). The reaction mixture was refluxed for 12 hours. After cooled to room temperature, the precipitates were collected by filtration and dissolved in water. The aqueous solution was acidified with 2 M HC1 (pH = 2). The resulting precipitates were collected by filtration and dried under reduced pressure to afford pyrazolo[l,5-a]pyrimidine- 5,7(4H,6H)-dione (649 g, 71percent) as a yellow solid, which was used for the next reaction without further purification. A stirred suspension of pyrazolo[l,5-a]pyrimidine-5,7(4H,6H)-dione (265 g, 1.75 mol) and NN-dimethylaniline (335.6 mL) in POCl3 (2.00 kg, 13.2 mol) was refluxed for 4 hours. After cooled to room temperature, the reaction mixture was poured into ice-water, and stirred for 30 min, neutralized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgSC>4, filtered and evaporated. The residue was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 : 10) to give 5,7- dichloropyrazolo[l,5-a]pyrimidine (287 g, 87percent) as a yellow solid. To a solution 5,7-dichloropyrazolo[l,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (313.5 g, 89percent) as light yellow solid. l NMR (300 MHz, CDCl3): δ ppm 7.04 (s, 1H), 8.21 (s, 1H); MS ESI [M + H]+ 265.9, calcd for [CgHzBrC Ns + H]+ 265.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium hydroxide; In water; at 90℃; for 0.5h; | 1 g of 5,7-dichloropyrazolo [2,5-a] pyrimidine was suspended in 25 mL of 1N aqueous sodium hydroxide solution and heated to 90 C,Stir for 0.5 h. The reaction was detected by thin layer chromatography, and after completion of the reaction, the reaction solution was cooled to room temperature.The solution was adjusted to pH = 2 with 1N HCl solution to give a suspension,5-chloropyrazolo [1,5-a] pyridine-7 (4H) -one (0.9 g, yield = 99%) was obtained by standing filtration. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 25℃; for 72h; | To a solution of the compound prepared in Preparative Example 123 (0.25 g, 1.3 MMOL) in dioxane (5 mL) was added IPR2NET (0.47 mL, 2.0 eq. ) and 3- aminomethylpyridine (0.15 ml, 1.1 eq. ). The resulting solution was stirred at room temperature 72 hours. The reaction mixture was diluted with H20 and extracted with EtOAc. The combined organics were washed with H20 and saturated NACI, dried over NA2S04, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography using a 5% MeOH in CH2CI2 solution as eluent (0.29 g, 83% yield). MS: MH+=260. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With trichlorophosphate; In N,N-dimethyl-aniline; for 4h;Reflux; | A stirred suspension of pyrazolo[ l ,5-a]pyrimidine-5,7(4H,6H)-dione (265 g, 1 .75 mol) and NN- dimethylaniline (335.6 mL) in POCl3(2.00 kg, 13.2 mol) was refluxed for 4 hours. After cooled to room temperature, the reaction mixture was poured into ice-water, and stirred for 30 min, neutralized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgS04, filtered and evaporated. The residue was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 : 10) to give 5,7-dichloropyrazolo[l ,5-a]pyrimidine (287 g, 87%) as a yellow solid. |
87% | With N,N-dimethyl-aniline; trichlorophosphate; for 4h;Inert atmosphere; Reflux; | To a stirred solution of sodium ethoxide in EtOH, which was prepared from sodium (281.3 g, 12.0 mol) and EtOH (10 L) by the conventional method, were added diethyl malonate (963.7 g, 6.02 mol) at ambient temperature and then compound lH-pyrazol-3-amine (500 g, 6.02 mol). The reaction mixture was refluxed for 12 hours. After cooled to room temperature, the precipitates were collected by filtration and dissolved in water. The aqueous solution was acidified with 2 M HC1 (pH = 2). The resulting precipitates were collected by filtration and dried under reduced pressure to afford pyrazolo[l,5-a]pyrimidine- 5,7(4H,6H)-dione (649 g, 71%) as a yellow solid, which was used for the next reaction without further purification. A stirred suspension of pyrazolo[l,5-a]pyrimidine-5,7(4H,6H)-dione (265 g, 1.75 mol) and NN-dimethylaniline (335.6 mL) in POCl3 (2.00 kg, 13.2 mol) was refluxed for 4 hours. After cooled to room temperature, the reaction mixture was poured into ice-water, and stirred for 30 min, neutralized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgSC>4, filtered and evaporated. The residue was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 : 10) to give 5,7- dichloropyrazolo[l,5-a]pyrimidine (287 g, 87%) as a yellow solid. To a solution 5,7-dichloropyrazolo[l,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (313.5 g, 89%) as light yellow solid. l NMR (300 MHz, CDCl3): delta ppm 7.04 (s, 1H), 8.21 (s, 1H); MS ESI [M + H]+ 265.9, calcd for [CgHzBrC Ns + H]+ 265.9. |
77% | With N,N-dimethyl-aniline; trichlorophosphate; at 5 - 60℃; | POC13 (62 mL) was cooled to 5 [C] under nitrogen and dimethylaniline (11.4 g, 2.8 eq. ) and the compound prepared in Preparative Example 33.10 (4.75 g, 0.032 mol). The reaction mixture was warmed to 60 [C] and stirred overnight. The reaction mixture was cooled to [30 C] and the POC13 was distilled off under reduced pressure. The residue was dissolved in [CH2CI2] (300 mL) and poured onto ice. After stirring 15 minutes, the pH of the mixture was adjusted to 7-8 with solid [NAHCO3.] The layers were separated and the organic layer was washed with H20 (3 x 200 mL), dried over [MGS04,] filtered, and concentrated. The crude product was purified by flash chromatography using a 50: 50 [CH2CI2 :] hexanes solution as eluent to elute the dimethyl aniline. The eluent was then changed to 75: 25 [CH2CI2] : hexanes to elute the desired product (4.58 g, 77% yield). MS: MH+=188. |
77% | With 2,3-Dimethylaniline; trichlorophosphate; at 60℃; | POCl3 (62 mL) was cooled to 5 C under nitrogen and dimethylaniline (11.4 g, 2.8 eq. ) and the compound prepared in Preparative Example 33.10 (4.75 g, 0.032 mol). The reaction mixture was warmed to 60 [C] and stirred overnight. The reaction mixture was cooled to 30 C and the POCI3 was distilled off under reduced pressure. The residue was dissolved in CH2CI2 (300 mL) and poured onto ice. After stirring 15 minutes, the pH of the mixture was adjusted to 7-8 with solid NaHCO3. The layers were separated and the organic layer was washed with H2O (3 x 200 mL), dried over MgSO4, filtered, and concentrated. The crude product was purified by flash chromatography using a 50: 50 CH2CI2 : hexanes solution as eluent to elute the dimethyl aniline. The eluent was then changed to 75: 25 CH2CI2 : hexanes to elute the desired product (4.58 g, 77% yield). MS: MH+=188. |
77% | With 2,3-Dimethylaniline; trichlorophosphate; at 5 - 60℃; | [POCI3] (62 mL) was cooled to 5 [C] under nitrogen and dimethylaniline (11.4 g, 2.8 eq. ) and the compound prepared in Preparative Example 39 (4.75 g, 0.032 [MOL).] The reaction mixture was warmed to 60 [C] and stirred overnight. The reaction mixture was cooled to 30 [C] and the POCI3 was distilled off under reduced pressure. The residue was dissolved in [CH2CI2] (300 mL) and poured onto ice. After stirring 15 minutes, the pH of the mixture was adjusted to 7-8 with [SOLID NAHC03.] The layers were separated and the organic layer was washed with H20 (3 x 200 mL), dried over [MGS04,] filtered, and concentrated. The crude product was purified by flash chromatography using a 50: 50 [CH2CI2] : hexanes solution as eluent to elute the dimethyl aniline. The eluent was then changed to 75: 25 [CH2CI2] : hexanes to elute the desired product (4.58 g, 77% yield). MS: [MH+=1 88.] |
77% | With N,N-dimethyl-aniline; trichlorophosphate; at 5 - 60℃; | POCI3 (62 mL) was cooled to 5 C under nitrogen and dimethylaniline (11.4 g, 2.8 eq. ) and the compound prepared in Preparative Example 75 (4.75 g, 0.032 MOL). The reaction mixture was warmed to 60 C and stirred overnight. The reaction mixture was cooled to 30 C and the POCI3 was distilled off under reduced pressure. The residue was dissolved in CH2CI2 (300 mL) and poured onto ice. After stirring 15 minutes, the pH of the mixture was adjusted to 7-8 with SOLID NAHC03. THE LAYERS were separated and the organic layer was washed with H20 (3 x 200 mL), dried over MGS04, filtered, and concentrated. The crude product was purified by flash chromatography using a 50: 50 CH2CI2 : hexanes solution as eluent to elute the dimethyl aniline. The eluent was then changed to 75: 25 CH2CI2 : hexanes to elute the desired product (4.58 g, 77% yield). MS: MU+=188. |
61.2% | With N,N-dimethyl-aniline; trichlorophosphate; at 80℃;Inert atmosphere; | Pyrazolo[1,5-a]pyrimidine-5,7(4H,6H)-dione (2) (20mmol, 1equiv) was added to the mixture of POCl3 (440mmol, 22equiv) and dimethylaniline (60mmol, 3equiv) in an ice-bath under nitrogen protection. The solution was stirred overnight at 80C and then cooled and concentrated. The obtained residue was dissolved in methylene chloride (50mL) and poured into ice-water. After being stirred for 10min, it was adjusted to pH 8?9 using solid NaHCO3. The organic layer was then separated, washed (water), dried (MgSO4), filtered and concentrated. The crude product was purified by flash chromatographic column to afford 5,7-dichloropyrazolo[1,5-a]pyrimidine (3) with a yield of 61.2% (EI-MS: 188.3 [M+H], 190.4 [M+H]). |
(2) Diethyl aniline(3.6 mL) and phosphorous oxychloride(9.3 mL) were added to 4H-pyrazolo[1,5-a]pyrimidine-5,7-dione(1.7 g) and the mixture was stirred at 70-75C for an hour. the reaction solution was concentrated under reduced pressure and azeotropically distilled with toluene twice. The half amount of the residue was dissolved in ethyl acetate, poured into ice and an aqueous saturated sodium bicarbonate solution and then extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified with silica gel column chromatography(hexane/ethyl acetate=19/1 to 4/1) to give 5,7-dichloro-pyrazolo[1,5-a]pyrimidine(0.54 g) as a colorless solid. APCI-MS(m/e):188/190[M+H]+. | ||
6.6 g | With N,N-diethylaniline; trichlorophosphate; for 4h;Reflux; | To a stirred solution of sodium ethoxide in EtOH, which was prepared from sodium (2.77 g, 120 mmol) and EtOH (90 mL) by the conventional method, were added diethyl malonate (9.64 g, 60 mmol) at ambient temperature and then 3-aminopyrazole (5.0 g, 60 mmol). The reaction mixture was refluxed for 24 h. After cooling to room temperature, the precipitates were collected by filtration and dissolved in water. The aqueous solution was acidified with 2 N HCl (pH ?2). The resulting precipitates were collected by filtration and dried under reduced pressure to afford 4H-pyrazolo[1,5-a]pyrimidine-5,7-dione (6.56 g) as a white powder, which was used for the next reaction without further purification. MS (FAB, Pos) m/z 152 (M+H)+CommentA stirred suspension of 4H-pyrazolo[1,5-a]pyrimidine-5,7-dione (6.56 g) and N,N-diethylaniline (8.3 mL, 52 mmol) in phosphorus oxychloride (30 mL) was refluxed for 4 h. After cooling, the reaction mixture was poured into ice-water, stirred for 30 min, neturalized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgSO4, and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/hexane (1/10) to give 38a (6.60 g, 81% yield in 2steps) as a yellow solid. TLC Rf = 0.51 (EtOAc/hexane, 1/3); 1H NMR (300 MHz, CDCl3) delta 8.23 (d, J = 2.4 Hz, 1H), 7.00 (s, 1H), 6.75 (d, J = 2.4 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-Bromosuccinimide; ammonium cerium(IV) nitrate; In acetonitrile; for 1.0h;Heating / reflux; | To a solution of 5, 7-CHLOROPYRAZOLO [1, 5-A] PYRIMIDINE (1 g, 5.32 MMOL) in ACETONITRILE (20 CM3) was added N-BROMOSUCCINIMIDE (1.04 g, 5. 85 MMOL) and ceric ammoinum nitrate (0.029 g, 0.053 MMOL). The reaction was heated at reflux for 1 hour. The reaction was washed with aqueous sodium metabisulfite (30 CM3, 10% solution) and then brine (20 cm3). The organic fraction was dried with magnesium sulphate and CONCENLRATED IN VACUO. The product was purified on silica ELUTING with 20% ETHYLACETAT in hexane, to yield the title compound as A yellow solid (1. 33 g, 92%). deltaH (400 MHz; d4-CDCl3) 8.22 (1H, s), 7.04 (1H, s). |
89% | With N-Bromosuccinimide; In acetonitrile; at 20℃; for 2.0h; | To a solution 5,7-dichloropyrazolo[l ,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (3 13.5 g, 89%) as light yellow solid. NMR (300 MHz, CDCl3): 5 7.04 (s, 1 H), 8.21 (s, 1 H); MS ESI [M + H]+265.9, calcd for [C6H2BrCl2N3+H]+265.9. |
89% | With N-Bromosuccinimide; In acetonitrile; at 20℃; for 2.0h;Inert atmosphere; | To a stirred solution of sodium ethoxide in EtOH, which was prepared from sodium (281.3 g, 12.0 mol) and EtOH (10 L) by the conventional method, were added diethyl malonate (963.7 g, 6.02 mol) at ambient temperature and then compound lH-pyrazol-3-amine (500 g, 6.02 mol). The reaction mixture was refluxed for 12 hours. After cooled to room temperature, the precipitates were collected by filtration and dissolved in water. The aqueous solution was acidified with 2 M HC1 (pH = 2). The resulting precipitates were collected by filtration and dried under reduced pressure to afford pyrazolo[l,5-a]pyrimidine- 5,7(4H,6H)-dione (649 g, 71%) as a yellow solid, which was used for the next reaction without further purification. A stirred suspension of pyrazolo[l,5-a]pyrimidine-5,7(4H,6H)-dione (265 g, 1.75 mol) and NN-dimethylaniline (335.6 mL) in POCl3 (2.00 kg, 13.2 mol) was refluxed for 4 hours. After cooled to room temperature, the reaction mixture was poured into ice-water, and stirred for 30 min, neutralized with saturated aqueous sodium carbonate and extracted with EtOAc. The combined organic layers were washed with water, brine and dried over MgSC>4, filtered and evaporated. The residue was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 : 10) to give 5,7- dichloropyrazolo[l,5-a]pyrimidine (287 g, 87%) as a yellow solid. To a solution 5,7-dichloropyrazolo[l,5-a]pyrimidine (246.6 g, 1.31 mol) in CH3CN (1.8 L) was added NBS (245 g, 1.38 mol ). The resulting mixture was stirred at room temperature for 2 hours. After removal of the solution, the reaction mixture was purified by column chromatography on silica gel (gradient: EtOAc/PE 1 :5) to give the title compound (313.5 g, 89%) as light yellow solid. l NMR (300 MHz, CDCl3): delta ppm 7.04 (s, 1H), 8.21 (s, 1H); MS ESI [M + H]+ 265.9, calcd for [CgHzBrC Ns + H]+ 265.9. |
With N-Bromosuccinimide; In chloroform;Heating / reflux; | A solution of the 5, 7-dichloropyrazolo [1, 5-a] pyrimidine (V-01) (0. 01 mol) in chloroform (50 mL) was treated with N-CHLOROSUCCINIMIDE, N-BROMOSUCCINIMIDE or iodine monochloride (0. 011 mol) at room temperature. The mixture was boiled under reflux until all solids were dissolved and no starting material remained (by TLC). The mixture was poured onto ice/water and the organic layer was separated, washed with aqueous NA2CO3, dried over MGS04, and the solvent removed in vacuo. The residual material was purified by chromatography over silica gel to provide the 3-halo-5, 7-DICHLOROPYRAZOLO [1, 5-A] PYRIMIDINE (V-02). | |
With sodium hydroxide; N-Bromosuccinimide; In chloroform; | EXAMPLE 14 3-Bromo-5,7-dichloropyrazolo(1,5-a)pyrimidine To a solution of 5.3 g of 5,7-dichloropyrazolo(1,5-a)pyrimidine in 70 ml of chloroform was added portionwise 6 g of N-bromosuccinimide while keeping the temperature below 40 C. The resulting solution was refluxed for 30 minutes and was then stirred at room temperature for 12 hours. The suspension was then filtered. The filtrate was washed with 50 ml of cold 10% sodium hydroxide aqueous solution twice and was then dried over MgSO4. The chloroform solution was then concentrated under reduced pressure to give 7.47 g of the desired product, m.p. 73-75 C. NMR(CDCl3)delta: 7.02 (s, 1H) and 8.18 (s, 1H). | |
With N-Bromosuccinimide;Heating / reflux; | Example 3; [A General Procedure for the Synthesis of a Pyrazolo[1,5-a]pyrimidine Derivative Represented by General Formula (V-04)]; A mixture was prepared by adding N-chlorosuccinamide, N-bromosuccinamide or iodine monochloride (0.011 mol) to a chloroform (50 mL) solution containing 5,7-dichloropyrazolo[1,5-a]pyrimidine (V-03) (0.01 mol) at room temperature. The mixture was stirred under heating and reflux until all solid was dissolved and the starting materials disappeared by TLC. The mixture was poured into ice/water to separate the organic layer, which was washed with aqueous Na2CO3 solution, subsequently dried with MgSO4, and the solvent was removed under vacuum. The residue was purified by silica gel chromatography to obtain 3-halo-5,7-dichloropyrazolol,5-alpyrimidine (V-04). The typical yield of the reaction ranged from 60 to 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In isopropyl alcohol; at 20℃; | To a solution of 5,7-dichloropyrazolo [1, 5-A] pyrimidine (IV) (2 g) and triethylamine (2 equivalents) in 2-propanol (20 ml) was added the amine R3NH2 (1 or 1.1 equivalents) and the mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was then partitioned between water and dichloromethane. The organic phase was washed twice with water and the combined aqueous phases back-extracted with dichloromethane. The combined organic layers were combined, washed with brine and dried over NA2SO4. Removal of the solvent in vacuo yielded the precursor (III). (Purification performed-normally the products did not require any further purification, if they did, they were recrystallised. Analysis performed-NMR, HPLC and MS.) | |
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; | To A solution of 5, 7-DICHLOROPYRAZOLO [1, 5-A] PYRIMIDINE (IV) (2 g) in 2-propanol (25 ml) containing N, N-DIISOPROPYLETHYLAMINE (2 equivalents) was added the amine RNHZ (1.2 equivalents). The reaction was heated overnight at 80 oC and the solvent removed in VACUO. The residue was partitioned between water and dichloromethane and the ORGANIC PHASE WAS WASHED WITH WATER, BRINE AND DRIED OVER MGS04. REMOVAL of the solvent in VACUA yielded the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In 1,4-dioxane; at 20℃; | (3); To compound (1) (10.85g) in 1,4-dioxane (200ml) were added 2,4-dichlorobenzylamine (15.2g) and triethylamine (14.6g) at room temperature, and the mixture was stirred overnight. After the reaction mixture was concentrated in vacuo, to the residue was added ethyl acetate and the mixture was washed with aqueous saturated sodium bicarbonate solution and saturated brine, and dried. After removal of the solvent, the residue was purified with silica gel column chromatography (hexane:ethyl acetate=4:1) to give compound (2) (18.0g) as a colorless powder. APCI-MS (m/e): 327/329 (M+H)+ | |
With triethylamine; In 1,4-dioxane; at 50 - 60℃; for 4h; | (3) 2,4-Dichlorobenzylamine(440 mg) and triethylamine(0.35 mL) were added to a solution of <strong>[57489-77-7]5,7-dichloro-pyrazolo[1,5-a]pyrimidine</strong>(470 mg) in 1,4-dioxane(5 mL) and the mixture was stirred at 50-60C for 4 hours. After standing to cool, an aqueous saturated sodium bicarbonate solution was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate and the solvent was distilled away. The residue was purified with silica gel column chromatography(hexane/ethyl acetate=9/1 to 4/1) to give (5-chloro-pyrazolo[1,5-a]pyrimidine-7-yl)-(2,4-dichlorobenzyl)-amine(697 mg) as a colorless solid. APCI-MS(m/e):327/329[M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.7% | Under nitrogen protection, 60% NaH (1.36g, 34mol) was slowly added to 60mL of cold N, N-dimethylformamide.The temperature was controlled to about 0 C, and 2-isopropylsulfonylaniline (4.10 g, 20.6 mmol) was slowly added, and the mixture was kept under stirring for 0.5 hours.To the above solution was added a solution of 5,7-dichloropyrazolo [1,5-a] pyrimidine (3.20 g, 17.0 mmol) in 10 mL of N, N-dimethylformamide,The reaction solution was slowly raised to room temperature and heated to 60 C for 8 hours.The reaction solution was poured into ice water, a solid was precipitated, and the crude product was filtered and dried.The crude product was recrystallized from isopropanol to obtain 4.10 g of 5-chloro-N- [2- (isopropylsulfonyl) phenyl] pyrazolo [1,5-a] pyrimidin-7-amine (c),The yield was 68.7%. | |
With sodium hydride; N,N-dimethyl-formamide; at 50℃; for 2h; | To a solution of 5, 7-dichloro-pyrazolo[l,5-a]pyrimidine (1.0 mmol) and 2- 0'sopropylsulfonyl)aniline(1.0 mmol) in 5 mL of DMF, was added carefully NaH (24 mg). The resulting suspension was stirred at 500C for 2 hours. After cooling at RT and careful quenching (ice), water was added and the mixture was extracted with EtOAc. The organic layers were collected, dried (Na2SO4), filtrated and concentrated. The residue was purified over SiO2 column chromatography (eluent: 9: 1 Hexane: EtOAc), to give the desired 5-chloro-N-(2- (isopropylsulfonyl)phenyl)pyrazolo[l,5-a]pyrimidin-7-amine. MS (ES+): 351.06 (M+l)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N,N-dimethyl-aniline; trichlorophosphate; at 20 - 60℃; for 16.0h;Inert atmosphere; | POC13 (130 mL) was added to <strong>[57489-70-0]pyrazolo[1,5-a]pyrimidine-5,7-diol</strong> (10g. 66 rnrnol). The suspension was cooJed to 0 C ard N,N-dimethylaniline (23 mL. 179 mmoi) was siowy added. After warming to room temperature, the reaction was heated at 60 C under N2 for 16 hr. Upon coohng, the reactior mixture was concentrated in aeuo to give a brown viscous liquid, which was slowly poured onto ice and aIowed to warm to room temperature. The pH was adjustedpH 8 with saturated NaHCO3. The organic layer was then extracted with CH2C12 (4 x 50 mL), dried (MgSO4), and concentrated in vacuo to give a brown ?iquid. Purification by flash column chromatography using 1:1 v/v DCM:hexanes to 2:1 v/v DCM:hexanes afforded the title compound (10.7 g, 86% yield) as a white crystalline solid. MS m/z 189.36 [M+1]. |
68% | With trichlorophosphate; In N,N-dimethyl-aniline; for 24.0h;Reflux; | Slowly add 5,7-dihydroxypyrazolo [1,5-a] pyrimidine (6.50 g, 43.0 mmol) to 60 mL of phosphorus oxychloride,Carefully add N, N-dimethylaniline (5.0 mL) and heat to reflux for 24 hours.Most of the solvent was removed by evaporation under reduced pressure, and the residue was slowly poured into ice water.Vigorously stir, precipitate a large amount of solid, suction filter, wash the filter cake with water to neutral, and dry to obtain a light yellow crude product.The crude product was separated by silica gel column chromatography to obtain 5.5 g of 5,7-dichloropyrazolo [1,5-a] pyrimidine (b) as a pale yellow solid with a yield of 68.0%. |
64% | With N,N-dimethyl-aniline; trichlorophosphate; at 0 - 60℃; for 16.0h;Inert atmosphere; | Step B - Synthesis of 5,7-dichloropyrazolo[ l,5-a]pyrimidine (lnt-9b)lnt-9a Int-thetabTo pyrazolo[l,5-aJpyrimidine-5,7-diol (Int-9a, 9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 ( 125 mL, 1341.1 mmol). The flask was then cooled to 0 0C and OC2009.701887N, N-dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction mixture was then heated at 60 0C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHCtheta3 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na?Stheta4) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50% CHbCb/hexanes (to elute aniline) followed by 75% CHaC^/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5-a]pyrimidine (Int-9b) as a white solid (7.7 g, 40.8 mmol, 64%). |
64% | To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2CI2 (4 x 50 mL), dried (Na2S04) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50% CHaCLVhexanes (to elute aniline) followed by 75% CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5~ a]pyrimidine as a white solid (7.7 g, 40.8 mmol, 64%). | |
36% | With trichlorophosphate; In N,N-dimethyl-aniline; at 80℃; | Dissolving 10 mmol of <strong>[57489-70-0]pyrazolo[1,5-a]pyrimidine-5,7-diol</strong> in 20 mL of phosphorus oxychloride,Then 1.0 mL of N,N-dimethylaniline was added.The mixture was heated to reflux at 80 C for 18-20 hours and cooled.Excess phosphorus phosphide is removed in vacuo,The residue was poured into cold water and extracted with CH 2Cl 2. Purified to obtain a compound5,7-Dichloro-pyrazolo[1,5-a]pyrimidine, yield: 36%. |
3-Amino-pyrazole (534 mg, 6.43 mM) was dissolved in sodium ethoxide (1M ethanol solution, 12.9 mL, 12.9 mM) and then diethyl malonate (1.07 mL, 7.07M) was added to the solution. This reaction liquid was stirred at 150 C. for 40 minutes under the irradiation with microwaves. This reaction mixture was diluted with water, acidified (pH 2) by the addition of hydrochloric acid and then extracted with ethyl acetate. The extracts were combined together, dried over anhydrous sodium sulfate and then the solvent was distilled off. Phosphoryl chloride (10 mL) was added to the resulting solid with ice-cooling and then the resulting suspension was stirred for 2 hours and a half, while refluxing the same with heating. The phosphoryl chloride was distilled off from this reaction liquid, ethanol was added to the resulting residue with ice-cooling and the mixture was subsequently stirred for 15 minutes. After the concentration of this reaction liquid, the latter was diluted with a saturated aqueous sodium bicarbonate solution and then extracted with methylene chloride. The extracts obtained were combined, dried over anhydrous sodium sulfate and then purified by the silica gel column chromatography (methylene chloride/hexane=3:1) to thus obtain the title compound (403 mg, overall yield of these two steps: 34%).1H-NMR (300 MHz, CDCl3): delta 6.74 (d, 1H, J=2.3 Hz), 6.99 (s, 1H), 8.22 (d, 1H, J=2.3 Hz); MS (ESI) m/z 188 (M+H)+. | ||
With N,N-dimethyl-aniline; trichlorophosphate; at 0 - 60℃; for 16.0h;Inert atmosphere; | To pyrazolo[l,5-a]pyrimidine-5,7-dioI (9.6 g, 63.5 mmol) in a 500 mL flask was added P0C13 (125 mL, 1341.1 mmol). The flask was then cooled to 0C and N5 N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2C12 (4 x 50 mL), dried (NajSO,,) and concentrated in vacuo to give a brown liquid (29.8 g). Gradient column chromatography on silica eluting with 50% CH2Cl2/hexanes (to elute aniline) followed by 75% CH2Cl2/hexanes (to elute product) gave 5,7- dichloropyrazolo[l,5-a]pyrimidine as a white solid. | |
With trichlorophosphate; In N,N-dimethyl-aniline; at 0 - 60℃; for 16.0h;Inert atmosphere; | To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2C12 (4 x 50 mL), dried (Na^SO^ and concentrated in vacuo to give a brown liquid. Gradient column chromatography on silica eluting with 50% CH2Cl2/hexanes (to elute aniline) followed by 75% CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l ,5-a3pyrimidine as a white solid. | |
With trichlorophosphate; at 0 - 60℃; for 16.0h;Inert atmosphere; | To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2C12 (4 x 50 mL), dried (Na2S0 ) and concentrated in vacuo to give a brown liquid. Gradient column chromatography on silica eluting with 50% CH2Cl2/hexanes (to elute aniline) followed by 75% CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5- ajpyrimidine as a white solid. | |
With N,N-dimethyl-aniline; trichlorophosphate; at 0 - 60℃; for 16.0h; | To pyrazolo[l,5-a]pyrimidine-5,7-diol (9.6 g, 63.5 mmol) in a 500 mL flask was added POCl3 (125 mL, 1341.1 mmol). The flask was then cooled to 0C and N, N- dimethylaniline (22 mL, 173.6 mmol) was carefully added. On warming to room temperature, the reaction was then heated at 60C under an atmosphere of argon for 16 hours. On cooling, the reaction mixture was concentrated in vacuo to give a brown viscous liquid. This brown viscous liquid was carefully poured onto ice and allowed to warm to room temperature overnight. To the brown solution was carefully added saturated NaHC03 solution until no further effervescence was observed and pH ~ 8 was attained. Organics were then extracted with CH2C12 (4 x 50 mL), dried (Na2S04) and concentrated in vacuo to give a brown liquid. Gradient column chromatography on silica eluting with 50% CH2Cl2/hexanes (to elute aniline) followed by 75% CH2Cl2/hexanes (to elute product) gave 5,7-dichloropyrazolo[l,5- a]pyrimidine as a white solid. | |
With trichlorophosphate; In N,N-dimethyl-aniline; for 24.0h;Reflux; | Solution of <strong>[57489-70-0]pyrazolo[1,5-a]pyrimidine-5,7-diol</strong> (6.50 g, 43.0 mmol) in phosphorus oxychloride (80 mL) was mixed with N N-dimethylaniline (5.0 mL), and the mixture was refluxed for 24 h. Excess phosphorus oxychloride was removed in vacuo. After cooling to room temperature, the residue was poured into ice water and extracted with EtOAc (3×100 mL). The combined organic phases were washed with 1 N HCl several times, until N,N-dimethylaniline was completely removed, and then washed with water and brine. The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was purifi ed by silica gel column chromatography to afford the compound 3 as a yellow solid, yield 68.0%. 1H NMR spectrum, delta, ppm: 8.23 d (1H, J = 3.0 Hz), 7.02 s (1H), 6.77 d (1H, J = 3.0 Hz). MS (ESI): m/z: 181.1 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With ammonium hydroxide; at 20 - 85℃;Sealed tube; | Step C - Synthesis of 5-chloropyrazolo[ 1 ,5-a]pyrimidin-7-amine (Int-9c)To 5,7-dichloropyrazolo[ 1 ,5-a]pyrimidine (Int-9b, 7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85 0C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free-flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5- a]pyrimidin-7-amine (Int-9c) as a yellow-tinged white solid (6.8 g, 40.3 mmol, 100%). |
100% | With ammonium hydroxide; at 85℃; for 2.5h;Sealed vessel; | To 5f7-dichIoropyrazolo[l,5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free- flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5-a]pyrimidin-7-amine as a yellow-tinged white solid (6.8 g, 40.3 mmol, 100%). |
88% | With ammonium hydroxide; at 85℃; for 12h;Reflux; | Example 1 Synthesis of 5-chloropyrazolo[1,5-a]pyrimidin-7-amine To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (3 g, 16 mmol) was added along with ammonium hydroxide solution (48 mL). The heterogeneous reaction was refluxed at 85 C. for 12 hours. After cooling to room temperature, the mixture was filtered, washed with water, and dried under vacuum overnight. The product, 5-chloropyrazolo[1,5-a]pyrimidin-7-amine, was collected as an off-white solid in 88% yield. LCMS (M+1=169) |
88% | With ammonium hydroxide; at 85℃; for 12h; | To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (3 g, 16 mmol) was added along with ammonium hydroxide solution (48 mL). The heterogeneous reaction was refluxed at 85 C. for 12 hours. After cooling to room temperature, the mixture was filtered, washed with water, and dried under vacuum overnight. The product, 5-chloropyrazolo[1,5-a]pyrimidin-7-amine, was collected as an off-white solid in 88% yield |
With ammonium hydroxide; at 85℃; for 2.5h;sealed tube; | To 5,7-dichloropyrazolo[l,5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free- flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5~a]pyrimidin-7-amine as a yellow-tinged white solid. | |
With ammonium hydroxide; at 85℃; for 2.5h; | To 5,7~dichloropyrazolo[l?5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free- flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5-a]pyrimidin-7-arnine as a yellow-tinged white solid. | |
With ammonium hydroxide; at 85℃; for 2.5h; | To 5,7-dichloropyrazolo[l,5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free- flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l,5-a]pyrimidin-7-amine as a yellow-tinged white solid. | |
With ammonium hydroxide; at 85℃; for 2.5h;Sealed tube; | To 5,7-dichloropyrazolo[l ,5-a]pyrimidine (7.6 g, 40.4 mmol) in a sealed vessel was added NH4OH (100 mL). The vessel was then sealed and heated at 85C for 2.5 hours, at which time the consistency of the white solid had changed (from foamy white solid to free- flowing white solid). The vessel was removed from the heat source and allowed to cool to room temperature overnight. On cooling, the contents of the vessel were collected and dried by vacuum filtration giving 5-chloropyrazolo[l ,5-a]pyrimidin-7-amine as a yellow-tinged white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triethylamine; In acetonitrile; at 80℃; | To 5,7-dichloropyrazolo[l,5-a]pyrimidine (200mg, 1.06mmol) in ACN was added Et3N (148mu1, 1.06mmol) and cyclopropanamine (75mu1, 1.06mmol). The reaction was refluxed at 80C overnight. The mixture was concentrated under reduced pressure, dissolved me DCM, and washed with water. The resulting organic layer was dried over Na2S04 and concentrated under reduced pressure to afford 156mg of 5-chloro-N- cyclopropylpyrazolo[l,5-a]pyrimidin-7-amine (70% yield). LCMS (M+l=209) |
70% | With triethylamine; In acetonitrile; at 80℃; | Example 7 Synthesis of 5-chloro-N-cyclopropylpyrazolo[1,5-a]pyrimidin-7-amine To <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (200 mg, 1.06 mmol) in ACN was added Et3N (148 mul, 1.06 mmol) and cyclopropylamine (75 mul, 1.06 mmol). The reaction was refluxed at 80 C. overnight. The mixture was concentrated under reduced pressure, dissolved in DCM, and washed with water. The resulting organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 156 mg of 5-chloro-N-cyclopropylpyrazolo[1,5-a]pyrimidin-7-amine (70% yield). LCMS (M+1=209) |
70% | With triethylamine; In acetonitrile; at 80℃; | To <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (200 mg, 1.06 mmol) in ACN was added Et3N (148 mul, 1.06 mmol) and cyclopropylamine (75 mul, 1.06 mmol). The reaction was refluxed at 80 C. overnight. The mixture was concentrated under reduced pressure, dissolved in DCM, and washed with water. The resulting organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 156 mg of 5-chloro-N-cyclopropylpyrazolo[1,5-a]pyrimidin-7-amine (70% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In 1,4-dioxane; at 1 - 30℃; for 0.5h; | 5,7-Dichloro-pyrazolo[1,5-a]pyrimidine (400 mg, 2.13 mM) was dissolved in 1,4-dioxane (8 mL), then morpholine (372 muL, 4.26 mM) was added to the solution and the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off from the reaction mixture, the resulting residue was diluted with water and extracted with methylene chloride. The extracts thus obtained were combined, dried over anhydrous sodium sulfate and the solvent was then distilled off to give the title compound (461 mg, yield: 91%). 1H-NMR (300 MHz, CDCl3): delta 3.77-3.80 (m, 4H), 3.93-3.96 (m, 4H), 6.07 (s, 1H), 6.50 (d, 1H, J=2.2 Hz), 8.02 (d, 1H, J=2.2 Hz); MS (ESI) m/z 239 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In 1-methoxy-2-propanol; at 110℃; for 1h;microwave irridation; | Step A: te/f-Butyl 4-(5-chloro-pyrazolo[1 ,5-a]pyrimidin-7-yl)piperazine-1-carboxylate 5,7-Dichloro-pyrazolo[1 ,5-a]pyrimidine (980 mg, 5.2 mmol) and te/f-butyl piperazine-1- carboxylate (2.3 g, 12.6 mmol) were dissolved in 1-methoxy-2-propanol (40 ml) and heated under microwave irridation at 110C for one hour. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica, pentane / ethylacetate). The raw product was crystallized from ethanol to yield 1.23 g of a crystalline solid (3.65 mmol, 70%). MS (APCI): m/z = 338.2 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N-chloro-succinimide; In chloroform; at 90℃; for 2.5h;Microwave irradiation; | To a solution of <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (2.0 g, 10.64 mmol) in CHC13 (l5mL) was added NCS (1.7Obg, 12.76 mmol). The mixture was heated to 90C under microwave irradiation for 2.5 hr. The solvent was removed in vacuo and the crude product was purified by flash column chromatography using a 9:1 v/v Hexanes:Ethyl acetate to afford the title compound (2.0 g, 90% yield) as a white crystalline solid. MS m/z 223.76 [M+1]. |
73.95% | With N-chloro-succinimide; In acetonitrile; at 0 - 20℃; for 2h; | Example 33a To a solution <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (200.0 mg, 1.06 mmol) in MeCN (5 mL) was added N-chlorosuccinimide (149.15 mg, 1.12 mmol) at 0 C. The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure, purified via column chromatography to give 3,5,7-trichloropyrazolo[1,5-a]pyrimidine (175 mg, 0.7867 mmol, 73.95% yield) as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.1% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.9% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.6% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.6% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h; | General procedure: 5,7-Dichloropyrazolo[1,5-a]pyrimidine (3, 2.5mmol, 1equiv) and appropriate substituted phenol (2.5mmol, 1equiv) and potassium carbonate (5mmol, 2equiv) were added to DMF, and then stirred for 12h at room temperature. After the reaction was ended, water was added to the mixture to give more precipitate. The crude product 5-chloro-7-subtitutedphenoxypyrazolo[1,5-a]pyrimidine (4-9) was obtained by filtration and desiccation with good yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | General procedure: To a well stirred 8-aminoquinoline (1 mmol) indry DMF (5 mL), sodium hydride (1.2 mmol, 60% in mineral oil) was added at 0 C.After 10 min stirring, the corresponding heterocyclic chloro compound (1.2mmol) was added and stirred for 10 min at rt then heated at 60 C for 5-12 h.Upon completion, the reaction mixture was poured into crushed ice and theresulting solid was filtered, washed with water and dried under vacuum. Thesolid was triturated with methanol and dried under vacuum to afford targetcompound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 80℃; for 16h;Inert atmosphere; | Under nitrogen, compound 5-a (400 mg, 1.04 mmol), <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (200 mg, 1.04 mmol) and sodium carbonate (331 mg, 3.12 mmol) were suspended in 1,4-dioxane (2 mL) and water (2 mL), Pd(dppf)Cl2 (100 mg, 0.1 mmol) was added. The mixture was heated to 80 C. and stirred for 16 hours. The mixture was concentrated under reduced pressure, the residue was treated with dichloromethane (20 mL), washed with water (10 mL×3) and saturated brine (10 mL) in sequence. The mixture was dried over anhydrous sodium sulfate, then filtrated, the filtrate was concentrated under reduced pressure, the residue was purified by preparation TLC (dichloromethane:ethyl acetate=30:1) to give compound 55-a (230 mg, yield: 54%). LC-MS (ESI): m/z=414 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine; In acetonitrile; at 20℃; for 3h; | Example 65 Synthesis of 7-(benzylthio)-5-chloropyrazolo[1,5-a]pyrimidine To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (4.1 g, 22 mmol) was added along with benzyl mercaptan (2.8 mL, 22 mmol), triethylamine (3.1 mL, 22 mmol), and acetonitrile (71 mL). The reaction was stirred at room temperature for 3 hours then diluted with water, filtered and washed with water. The product, 7-(benzylthio)-5-chloropyrazolo[1,5-a]pyrimidine, was collected as a solid in 96% yield after drying under vacuum overnight. LCMS (M+1=276) |
96% | With triethylamine; In acetonitrile; at 20℃; for 3h; | To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (4.1 g, 22 mmol) was added along with benzyl mercaptan (2.8 mL, 22 mmol), triethylamine (3.1 mL, 22 mmol), and acetonitrile (71 mL). The reaction was stirred at room temperature for 3 hours then diluted with water, filtered and washed with water. The product, 7-(benzylthio)-5-chloropyrazolo[1,5-a]pyrimidine, was collected as a solid in 96% yield after drying under vacuum overnight |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine; In acetonitrile; at 100℃; for 12h; | Example 48 Synthesis of tert-butyl 4-(5-chloropyrazolo[1,5-a]pyrimidin-7-ylamino)piperidine-1-carboxylate To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (896 mg, 4.8 mmol) was added along with tert-butyl 4-aminopiperidine-1-carboxylate (954 mg, 4.8 mmol), triethylamine (664 muL, 4.8 mmol), and acetonitrile (16 mL). The reaction was heated at 100 C. for 12 hours then cooled to room temperature, diluted with water, filtered and washed with water. The product, tert-butyl 4-(5-chloropyrazolo[1,5-a]pyrimidin-7-ylamino)piperidine-1-carboxylate, was collected as a solid in quantitative yield and dried under vacuum overnight. LCMS (M+1=352) |
With triethylamine; In acetonitrile; at 100℃; for 12h; | To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (896 mg, 4.8 mmol) was added along with tert-butyl 4-aminopiperidine-1-carboxylate (954 mg, 4.8 mmol), triethylamine (664 muL, 4.8 mmol), and acetonitrile (16 mL). The reaction was heated at 100 C. for 12 hours then cooled to room temperature, diluted with water, filtered and washed with water. The product, tert-butyl 4-(5-chloropyrazolo[1,5-a]pyrimidin-7-ylamino)piperidine-1-carboxylate, was collected as a solid in quantitative yield and dried under vacuum overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 60℃; for 4h; | Example 93 Synthesis of 3-((7-chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (452 mg, 2.4 mmol) was added along with (3-cyanobenzyl)zinc(II) bromide (6 mL, 3.75 mmol, 0.625M in DMF), Pd(PPh3)4 (110 mg, 0.1 mmol), and DMF (10 mL). The reaction was heated at 60 C. for 4 hours then cooled to room temperature. The reaction mixture was poured into saturated aqueous NH4Cl solution and ice and extracted with ethyl acetate. The combined extracts were washed with water, saturated NaCl solution, and then dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by column chromatography on silica using 35% ethyl acetate/hexanes as the eluent. The product, 3-((7-chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile, was recovered in 64% yield. LCMS (M+1=269) |
64% | With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 60℃; for 4h; | To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (452 mg, 2.4 mmol) was added along with (3-cyanobenzyl)zinc(II) bromide (6 mL, 3.75 mmol, 0.625M in DMF), Pd(PPh 3) 4 (110 mg, 0.1 mmol), and DMF (10 mL). The reaction was heated at 60 C. for 4 hours then cooled to room temperature. The reaction mixture was poured into saturated aqueous NH 4Cl solution and ice and extracted with ethyl acetate. The combined extracts were washed with water, saturated NaCl solution, and then dried over Na 2SO 4. The solvent was removed in vacuo and the residue was purified by column chromatography on silica using 35% ethyl acetate/hexanes as the eluent. The product, 3-((7-chloropyrazolo[1,5-a]pyrimidin-5-yl)methyl)benzonitrile, was recovered in 64% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With dmap; triethylamine; In acetonitrile; at 85℃; for 12h; | Example 285 Synthesis of tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (3.2 g, 17 mmol) was added along with 2-morpholinopropan-1-amine (2.4 g, 17 mmol), triethylamine (2.3 mL, 17 mmol), and acetonitrile (56 mL). The reaction was stirred at 85 C. for 12 hours then cooled to room temperature, diluted with water, filtered and washed with water. The intermediate, 5-chloro-N-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidin-7-amine, was dried under vacuum to provide 3.8 grams of an off-white solid (77% yield). LCMS (M+1=296) To 5-chloro-N-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidin-7-amine (3.8 g, 13 mmol) in methylene chloride (50 mL) was added triethylamine (2.1 mL, 15 mmol), dimethylaminopyridine (200 mg, 1.6 mmol), and di-t-butyldicarbonate (3.3 g, 15 mmol). The mixture was stirred at room temperature for 10 hours. The reaction mixture was transferred to a separatory funnel, washed 1* with H2O, 2* with brine, dried over MgSO4, filtered, and evaporated to dryness to provide an oily residue which solidified on standing. The product, tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate, was recovered as an off-white solid in 39% yield (5.1 mmol). LCMS (M+1=396) |
77% | With triethylamine; In acetonitrile; at 85℃; for 12h; | To the reaction flask, <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (3.2 g, 17 mmol) was added along with 2-morpholinopropan-1-amine (2.4 g, 17 mmol), triethylamine (2.3 mL, 17 mmol), and acetonitrile (56 mL). The reaction was stirred at 85 C. for 12 hours then cooled to room temperature, diluted with water, filtered and washed with water. The intermediate, 5-chloro-N-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidin-7-amine, was dried under vacuum to provide 3.8 grams of an off-white solid (77% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In <i>tert</i>-butyl alcohol at 100℃; for 6h; | 85 Synthesis of tert-butyl 3-(5-chloropyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate To the reaction flask, 5,7-dichloropyrazolo[1,5-a]pyrimidine (1.6 g, 8.2 mmol) was added along with tert-butyl 3-aminobenzoate (1.7 g, 8.7 mmol), triethylamine (1.2 mL, 8.6 mmol), and t-butyl alcohol (22 mL). The reaction was heated at 100° C. for 6 hours then diluted with water, filtered and washed with water. The product, tert-butyl 3-(5-chloropyrazolo[1,5-a]pyrimidin-7-ylamino)benzoate, was collected as a solid in quantitative yield after drying under vacuum overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With N,N-dimethyl-aniline; trichlorophosphate; at 5 - 60℃; for 12h;Inert atmosphere; | In a nitrogen stream at 5 C, to 4,5-dihydropyrazolo[1,5-a]pyrimidine-5,7-diol (40.8 g, 0.31 mol), POCl3 (100ml, 10.9 mmol) and dimethylaniline (120 mL, 0.94 mol) were mixed and stirred under reflux for 12 hours at 60 C. after the reaction was terminated to obtain a solid product was filtered after cooling to room temperature. The solid product then was dissolved in dichloromethane, was added dropwise to ice-water, which was then neutralized such that the rear 15 bungan stirred, pH 8 ~ 9 degree with solid NaHCO3. Then, the organic layer was extracted with dichloromethane and filtered into a MgSO4. After removal of the solvent from the obtained organic layer was purified by column chromatography (Hexane: MC = 3: 1 (v/v)) to give Compound I-1 (46.1 g, yield 77%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 6h;Inert atmosphere; | A solution of 5,7-dichloropyrazolo[1,5-ajpyrimidine (0.5 g, 2.66 mmol), (2- fluoro-4-methoxyphenyl)boronic acid (0.452 g, 2.66 mmol), and C52CO3 (1.733 g, 5.32 mmol) in 1,4-dioxane (10 mL) and water (1 mL) was purged with nitrogen gas for 30 mm. PdC12(dppf)-CH2C12 adduct (0.217 g, 0.266 mmol) was added to thereaction mixture and the solution was purged with nitrogen gas again for 10 mm. The reaction mixture was heated at 80 C for 6 h. The reaction mixture was concentrated and the residue obtained was dissolved in ethyl acetate (50 mL) and water (30 mL). The biphasic mixture was filtered through diatomaceous earth. The diatomaceous earth was washed with ethyl acetate (50 mL). The organic layer wasseparated, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford cmde product as a brown solid which was purified by silica gel-column chromatography (EtOAc in pet ether) to afford S-chloro-7-(2-fluoro-4- methoxyphenyl) pyrazolo [1,5-aj pyrimidine (0.52 g, 1.873 mmol, 70% yield) as a off-white color solid. LCMS (ESI) m/e 278.0 [(M+H) , calcd for C13H10C1FN3O278.Oj; LC/MS retention time (Method C): tR = 1.05 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With trichlorophosphate; | 5,7-Dichloropyrazolo[1,5-a]pyrimidine (J2) POCl3 (10 mL, 109 mmol) was added to a mixture of J1 (800 mg, 5.29 mmol) and dimethyl aniline (1.8 g, 14.82 mmol) in an ice-cooled round-bottom flask. The reaction mixture was stirred at room temperature for 10 min and then heated to 60 C for 3 h. The excess POCl3 was removed in vacuo, and the resulting residue was poured onto ice water. The aqueous solution was basified to pH=9 with solid NaHCO3. The mixture was extracted with EtOAc (3x100 mL). The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The resulting residue was purified by gradient elution on silica gel (20 to 80% EtOAc in heptane) to afford the title compound as a white solid (810 mg, 81%). 1H NMR (300 MHz, CDCl3): delta 8.22 (d, J = 3.0 Hz, 1H), 7.00 (s, 1H), 6.76 (d, J = 3.0 Hz, 1H) ppm; LRMS m/z (M+H) 188.1 found, 188.0 required. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h; | To a stirred solution of 3-hydroxy-N-phenylbenzamide 2 (598 mg, 2.81 mmol) in DMF (0833) (10 mL) at RT, were added 5,7-dichloropyrazolo[l,5-a]pyrimidine 1 (500 mg, 2.67 mmol) followed by K2C03 (553 mg, 4.01 mmol). The mixture was stirred at RT for 16 h. The reaction mixture was quenched with water (30 mL) and the precipitated solid was collected by filtration, washed with water (20 mL), and dried under vacuum to afford compound 3 (800 mg, 82%) as a pale yellow solid. 1H MR (500 MHz, OMSO-d6): delta 10.32 (s, 1H), 8.35 (d, J= 2.0 Hz, 1H), 8.01 - 8.07 (m, 2H), 7.73 - 7.78 (m, 4H), 7.36 (t, J= 8.0 Hz, 2H), 7.12 (t, J= 7.4 Hz, 1H), 6.77 (d, J = 2.3 Hz, 1H), 6.19 (s, 1H); LCMS Mass: 364.9 (M++l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h; | To a stirred solution of phenol (302 mg, 3.21 mmol) in DMF (10 mL) at RT, were added K2C03 (532 mg, 3.85 mmol) and 5,7-dichloropyrazolo[l,5-a]pyrimidine 1 (600 mg, 3.21 mmol). The mixture was stirred at RT for 16 h. The reaction mixture was diluted with water (30 mL) and extracted with EtOAc (2 chi 30 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2S04), filtered, and concentrated under reduced pressure. The residue was purified (silica gel; eluting with 40-50% EtOAc in hexanes) to afford compound 2 (700 mg, 89%) as an off-white solid. LCMS Mass: 245.9 (M++l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.95% | With trichlorophosphate; at 60℃; for 2.0h; | To a solution of 58.2 (15.0 g, 99.33 mmol, 1.0 eq)58.2 (38.5 g, 240.96 mmol, 1.0 eq) in Dimethylamine (90 mE) was added Phosphoryl chloride (18.23 g, 119.19 mmol, 1.2 eq) and stirred at 60 C. for 2 h. After completion of reaction, reaction mixture was cooled to room temperature, transferred into water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was furtherpurified by column chromatography and compound was eluted in 20% ethyl acetate in hexane to obtain pure 58.3. (11.0 g, Yield: 58.95%). MS(ES): mlz 190.96 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.32% | With N-iodo-succinimide; In acetonitrile; at 0 - 20℃; | To a solution of 58.3 (5.0 g, 26.59 mmol, 1.0 eq) in acetonitrile (50 mE), were added N-Iodo-succinimide (7.17 g, 31.90 mmol, 1.2. eq) at 00 C. The reaction mixture was stirred at room temperature for overnight. After completion of reaction, reaction mixture was transferred to ice cold water and product was extracted with dichloromethane. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by 20% ethyl acetate in hexane to obtain 58.4. (3.7 g, Yield:44.32%). MS (ES): mlz 314.86 [M+H]. |
9.1 g | With N-iodo-succinimide; In acetonitrile; for 1h;Reflux; | A mixture of <strong>[57489-77-7]5,7-dichloropyrazolo[1,5-a]pyrimidine</strong> (6.1 g, 32.4 mmol) and NIS (8.03 g,35,7 mmcl) in MeCN (20 ml) was heated under reflux for 1 h. The mixture wasconcentrated in vacuo and the residue dissolved in DCM (200 ml) and washed with water(200 ml). The organic phase was dried over Na2SO4(s), filtered and concentrated invacuo. Purification by column chromatography (220 g cartridge, DCM) afforded the titlecompound (9.1 g, 28.4 mmol, 98% purity) as a crystalline yellow solid. 1H NMR (400MHz, DMSO-d6) O 8.48 (s, 1H), 7.73 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | In isopropyl alcohol; at 79.84℃; for 15h; | Mix 5.0 mmol of <strong>[57489-77-7]5,7-dichloro-pyrazolo[1,5-a]pyrimidine</strong> with 50 mL of 2-propanol solution containing 10 mmol of N,N-dimethyl-1,3-propanediamine and stir. After heating at 353 K for 15 hours, it was cooled to room temperature; the obtained mixture was taken from ethyl acetate. EtOAc was evaporated. :ethyl acetate = 10:1) Purification gave compound NCPS.NCPS has the following properties: yellow powder, yield: 58%, melting point: 91-93 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In isopropyl alcohol; at 79.84℃; for 15h; | Mix 5.0 mmol of <strong>[57489-77-7]5,7-dichloro-pyrazolo[1,5-a]pyrimidine</strong> with 50 mL of 2-propanol solution containing 10 mmol of 1-methylpiperazine and stir.353K heating for 15 hours and then cooling to room temperature;The resulting reaction was extracted with ethyl acetate.The organic phase was taken and the organic phase was washed with water and aqueous sodium chloride and dried over anhydrous Na2SO?Concentrated in vacuo and purified by silica gel column chromatography (hexane: ethyl acetate=10:1)The compound CMPS was obtained.CMPS has the following properties: yellow powder, yield: 67%, melting point: 114-116 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.26% | With sodium hydride In N,N-dimethyl-formamide at 0 - 50℃; | 3.3.14. 5-chloro-N-(5-chloropyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine (3n): To a solution of 5-chloropyridin-2-amine (136.8 mg, 1.06 mM) in DMF (5 mL) was cooled to 0oC and added with NaH (60%, 63.8 mg, 1.6 mM) in portions. 5,7-dichloropyrazolo[1,5-a]pyrimidine (200 mg, 1.06 mM) was added in one portion. The reaction was allowed to r.t. and heated at 50oC. TLC was used to monitored the reaction until full conversion of the starting materials was detected. The reaction was cooled to 0oC and EA in PE to obtain 5-chloro-N-(5-chloropyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7- quenched with quenched with saturated NH4Cl solution. The mixture was extracted with ethyl acetate (30 mL) ×3. The organic phase was dried over Na2SO4 and concentrated to obtain the crude product. The crude was purified by F.C.C with 0% - 50% amine (0.26 g, yield: 87.26%); 1H NMR (400 MHz, CHLOROFORM-d) δ 8.86 (br. s., 1H), 8.42 (br. s., 1H), 7.96 - 8.10 (m, 1H), 7.93 (br. s., 1H), 7.71 (br. d, J = 1.00 Hz, 1H), 7.02 (d, J = 16.43 Hz, 1H), 6.55 (br. s., 1H); HRMS (ESI): calcd for C11H8Cl2N5 [M + H]+ 280.0157; found 280.0159. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); In acetonitrile; at 60 - 70℃; | To a solution of 5,7-dichloropyrazolo[1,5-a]pyrimidine (500 mg, 2.66 mmol, 1 equiv) in ACN (12.0 mL) was added Selectfluor (942 mg, 2.66 mmol, 1 equiv). The reaction mixture was heated to 60 C and stirred overnight. The reaction was then stirred at 70 C for 1 h and 45 min. Additional Selectfluor (300 mg, 0.847 mmol) was added and the solution was stirred at 70 C for 3 days. Additional Selectfluor (300 mg, 0.847 mmol) was again added and the reaction was stirred at 70 C for 1 h and 30 minutes. After cooling to room temperature, the reaction mixture was quenched carefully with saturated sodium bicarbonate until gas formation ceased. The solution was diluted with water and extracted with EtOAc (3x). The organic fractions were combined, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-80% DCM in hexanes) to afford the title compounds as a mixture. 3,5,7-trichloropyrazolo[1,5-a]pyrimidine was carried through the proceeding reactions as a side-product. Intermediate 3995,7-dichloro-3-fluoropyrazolo[1,5-a]pyrimidine ES/MS m/z: 206.0 [M+H].1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 3.3 Hz, 1H), 7.71 (s, 1H).19F NMR (376 MHz, DMSO-d6) δ -180.70. | |
With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate); In acetonitrile; at 60 - 70℃; | To a solution of 5,7-dichloropyrazolo[1,5-a]pyrimidine (500 mg, 2.66 mmol, 1 equiv) in ACN (12.0 mL) was added Selectfluor (942 mg, 2.66 mmol, 1 equiv). The reaction mixture was heated to 60 C and stirred overnight. The reaction was then stirred at 70 C for 1 h and 45 min. Additional Selectfluor (300 mg, 0.847 mmol) was added and the solution was stirred at 70 C for 3 days. Additional Selectfluor (300 mg, 0.847 mmol) was again added and the reaction was stirred at 70 C for 1 h and 30 minutes. After cooling to room temperature, the reaction mixture was quenched carefully with saturated sodium bicarbonate until gas formation ceased. The solution was diluted with water and extracted with EtOAc (3x). The organic fractions were combined, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-80% DCM in hexanes) to afford the title compounds as a mixture. 3,5,7-trichloropyrazolo[1,5-a]pyrimidine was carried through the proceeding reactions as a side-product. Intermediate 3995,7-dichloro-3-fluoropyrazolo[1,5-a]pyrimidine ES/MS m/z: 206.0 [M+H].1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 3.3 Hz, 1H), 7.71 (s, 1H).19F NMR (376 MHz, DMSO-d6) δ -180.70. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 1h; | A solution of 5,7-dichloropyrazolo[1,5-a]pyrimidine (100 mg, 0.53 mmol, 1 equiv), 3-Hydroxy-3-methylpyrrolidine hydrochloride (59 mg, 0.59 mmol, 1.1 equiv), DIPEA (0.095 mL, 0.53 mmol, 1 equiv), and MeCN (1 mL) was heated to 85oC. After 1 h, the reaction mixture was filtered, concentrated and directly purified by SiO2 chromatography (0-20% MeOH/DCM), affording 1-(5-chloropyrazolo[1,5-a]pyrimidin-7-yl)-3-methylpyrrolidin-3-ol. ES/MS m/z: 254.1 [M+H]. | |
With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 1h; | A solution of 5,7-dichloropyrazolo[1,5-a]pyrimidine (100 mg, 0.53 mmol, 1 equiv), 3-Hydroxy-3-methylpyrrolidine hydrochloride (59 mg, 0.59 mmol, 1.1 equiv), DIPEA (0.095 mL, 0.53 mmol, 1 equiv), and MeCN (1 mL) was heated to 85oC. After 1 h, the reaction mixture was filtered, concentrated and directly purified by SiO2 chromatography (0-20% MeOH/DCM), affording 1-(5-chloropyrazolo[1,5-a]pyrimidin-7-yl)-3-methylpyrrolidin-3-ol. ES/MS m/z: 254.1 [M+H]. |
Tags: 57489-77-7 synthesis path| 57489-77-7 SDS| 57489-77-7 COA| 57489-77-7 purity| 57489-77-7 application| 57489-77-7 NMR| 57489-77-7 COA| 57489-77-7 structure
[ 779353-64-9 ]
5,7-Dichloro-3-ethylpyrazolo[1,5-a]pyrimidine
Similarity: 0.90
[ 845895-95-6 ]
5,7-Dichloropyrazolo[1,5-a]pyrimidine-3-carbonitrile
Similarity: 0.86
[ 114040-06-1 ]
3-Bromo-5,7-dichloropyrazolo[1,5-a]pyrimidine
Similarity: 0.86
[ 58347-49-2 ]
7-Chloropyrazolo[1,5-a]pyrimidine
Similarity: 0.85
[ 29274-24-6 ]
5-Chloropyrazolo[1,5-a]pyrimidine
Similarity: 0.83
[ 779353-64-9 ]
5,7-Dichloro-3-ethylpyrazolo[1,5-a]pyrimidine
Similarity: 0.90
[ 845895-95-6 ]
5,7-Dichloropyrazolo[1,5-a]pyrimidine-3-carbonitrile
Similarity: 0.86
[ 114040-06-1 ]
3-Bromo-5,7-dichloropyrazolo[1,5-a]pyrimidine
Similarity: 0.86
[ 58347-49-2 ]
7-Chloropyrazolo[1,5-a]pyrimidine
Similarity: 0.85
[ 29274-24-6 ]
5-Chloropyrazolo[1,5-a]pyrimidine
Similarity: 0.83
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 :