Home Cart Sign in  
Chemical Structure| 612501-81-2 Chemical Structure| 612501-81-2

Structure of 612501-81-2

Chemical Structure| 612501-81-2

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 612501-81-2 ]

CAS No. :612501-81-2
Formula : C25H28ClFN4O4
M.W : 502.97
SMILES Code : O=C(N1CCC(OC2=CC3=C(NC4=CC=CC(Cl)=C4F)N=CN=C3C=C2OC)CC1)OC(C)(C)C

Safety of [ 612501-81-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Application In Synthesis of [ 612501-81-2 ]

* 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.

  • Downstream synthetic route of [ 612501-81-2 ]

[ 612501-81-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 612501-52-7 ]
  • [ 141699-59-4 ]
  • [ 612501-81-2 ]
YieldReaction ConditionsOperation in experiment
95% Step 2: Preparation OF TERT-BUTVL 4-R4- 3-CHLORO-2-FLUOROANILINO)-7-METHOXVQUINAZOLIN-6- YLOXVLPIPERIDINE-1-CARBOXYLATE; 4- (3-CHLORO-2-FLUOROANILINO)-6-HYDROXY-7-METHOXYQUINAZOLINE (116.7 g), tert-butyl 4-methylsulfonyloxypiperidine 1-carboxylate (153.1 g), potassium carbonate (75.7 g) and NMP (700 ml), were stirred at 100C to 105C, under nitrogen, for 24 hours. The mixture was cooled to 75C to 80C before water (1080 ml) was added whilst maintaining the temperature above 70C. The mixture was stirred at 70C to 75C for 90 minutes then cooled to 20C to 25C. The resulting solid was filtered, washed with water (2 x 175 ml), and then dried in the vacuum oven between 50C and 55C to give tert-butyl 4- [4- (3-CHLORO-2- FLUOROANILINO) -7-METHOXYQUINAZOLIN-6-YLOXY] PIPERIDINE-1-CARBOXYLATE ; (174.4 G; 95% YIELD); Melting point: 192-193. 5C ; NMR Spectrum: (DMSO d6) 1.40-1. 42 (d, 9H); 1.62-1. 72 (m, 2H); 1.99-2. 08 (m, 2H); 3.24-3. 33 (m, 2H); 3.65-7. 73 (m, 2H); 4.00 (s, 3H); 4.76 (m 1H) ; 7.28 (s; 1H); 7.37 (t, 3H); 7.56 (t, 1H) ; 7.63 (t, 1H); 8.01 (s, 1H); 8.72 (s 1H); Mass Spectrum: (M+H) + 503.
84% With potassium carbonate; In ethanol; water; for 16.5h;Reflux;Product distribution / selectivity; Step 1: 6-[(1-tert-Butoxycarbonyl)piperidin-4-yl]oxy}-4-(3-chloro-2-fluoroanilino)-7-methoxy quinazoline4-(3-Chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (prepared as described in Step 2 of Example A; 60.00 g, 0.1828 mol), tert-Butyl(4-methanesulfonyloxy)piperidine-1-carboxylate (88.04 g, 0.3107 mol) and potassium carbonate (30.31 g, 0.2193 mol) were suspended in ethanol (584 ml) and water (58 ml), and the mixture was heated to reflux with stirring. Heating was continued at reflux for 16.5 hours. The mixture was then cooled to 70 C. and water (234 ml) was added over 60 minutes.The batch was stirred at 65 C. for a further 2 hours to establish crystallisation. The slurry was cooled to 20 C. over 6 hours. The product was isolated by filtration. The filter cake was slurried with aqueous ethanol (ethanol 117 ml, water 58 ml) and then displacement washed with aqueous ethanol (ethanol 117 ml, water 58 ml). The filter cake was then slurried with water (175 ml) and then displacement washed with water (175 ml). The product was dried in vacuo at 40 C. to give the title compound (81.5 g, 84%); 1H NMR (500 MHz, DMSO-d6) delta ppm 1.42 (s, 9H) 1.60-1.70 (m, 2H) 1.96-2.04 (m, 2H) 3.23-3.30 (m, 2H) 3.65-3.75 (m, 2H) 3.95 (s, 3H) 4.68-4.75 (m, 1H) 7.24 (s, 1H) 7.29 (t, J=8.06 Hz, 1H) 7.49 (t, J=7.50 Hz, 1H) 7.54 (t, J=7.19 Hz, 1H) 7.88 (s, 1H) 8.39 (s, 1H) 9.57 (s, 1H); Mass Spectrum: 503.5, 505.5.
60% With cesium fluoride; In N,N-dimethyl acetamide; at 85℃; for 12h; To a solution of compound 7 (1.44 g, 4.51 mmol) in DMA (15 mL) was added compound 8 (378 mg, 1.35 mmol) and CsF (685 mg, 4.51 mmol). The reaction mixture was heated to 85 C and stirred. At intervals of 2 h, 4 h and 6 h, each time compound 8 (378 mg, 1.35 mmol) and CsF (685 mg, 4.51 mmol) were added. After the final addition,the reaction mixture was stirred at 85 C for further 6 h. The solvent was removed under vacuum and the residual was partitioned between CH2Cl2 and water. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by column chromatography with MeOH/CH2Cl2 (1:25) to afford 9 (1.37 g, 60%) as a pale yellow solid, mp 200-201 C. 1H NMR (DMSO-d6): d 9.59 (s, 1H), 8.39 (s, 1H), 7.88 (s, 1H), 7.55-7.48 (m, 2H), 7.29 (t, J = 8.0 Hz, 1H), 7.24 (s, 1H), 4.71 (s, 1H), 3.95 (s, 3H), 3.71-3.69 (m, 2H), 3.29-3.26 (m, 2H), 2.01-1.99 (m, 2H), 1.68-1.62 (m, 2H), 1.42 (s, 9H). LC-MS (ESI, m/z): calcd for C25H29ClFN4O4 ([M+H]+) 503.2, found 503.1.
58% With cesium fluoride; In N,N-dimethyl acetamide; at 85℃; for 18h; 4- (3-CHLORO-2-FLUOROANILINO)-6-HYDROXY-7-METHOXYQUINAZOLINE from Step 2 (1870 mg, 5.85 mmol) was dissolved in DMA (50 ml). tert-Butyl (4-methanesulfonyloxy) piperidine-1- carboxylate (prepared as in Chemical & Pharmaceutical Bulletin 2001,49 (7), 822-829; 490 mg, 1.76 mmol) and cesium fluoride (890 mg, 5.85 mmol) were added, and the mixture was heated to 85C with stirring. At intervals of 2 hours, 4 hours and 6 hours, tert-butyl 4- METHANESULFONYLOXYPIPERIDINE-1-CARBOXYLATE and cesium fluoride were added in the above quantities to the reaction mixture. Heating was continued at 85C for a further 6 hours after the final addition. The solvent was evaporated, and the residue was partitioned between DCM (150 ml) and H20 (150 ML). The aqueous layer was extracted with DCM (4x 100 ml), and the extractions combined with the DCM layer. The combined DCM fractions were dried over MGS04 and evaporated. The residue was purified by chromatography, eluting with 0 to 2.5% (7: 1 MEOH/CONCENTRATED aqueous NH4OH) in DCM. The appropriate fractions were combined and evaporated, giving the product as a light brown foam (2.40 g, 58%, allowing for 2.3 equivalents of residual DMA).'H NMR : 1.40 (s, 9H), 1.60-1. 65 (m, 2H), 1.95-2. 00 (m, 2H), 3.20-3. 25 (m, 2H), 3.65-3. 70 (m, 2H), 3.92 (s, 3H), 4.68 (m, 1H), 7.21 (s, 1H), 7.27 (dd, 1H), 7.47 (ddd, 1H), 7.51 (dd, 1H), 7.85 (s, 1H), 8.36 (s, 1H), 9.53 (s, 1H) ; Mass Spectrum: 503.5, 505.5.
58% With cesium fluoride; In N,N-dimethyl acetamide; at 85℃; for 18h; 4- (3-CHLORO-2-FLUOROANILINO)-6-HYDROXY-7-METHOXYQUINAZOLINE from Step 2 (1870 mg, 5.85 mmol) was dissolved in DMA (50 ml). tert-Butyl (4-methanesulfonyloxy) PIPERIDINE-1-CARBOXYLATE (prepared as in Chemical & Pharmaceutical Bulletin 2001,49 (7), 822-829; 490 mg, 1.76 mmol) and cesium fluoride (890 mg, 5.85 mmol) were added, and the mixture was heated to 85C with stirring. At intervals of 2 hours, 4 hours and 6 hours, tert-butyl 4-METHANESULFONYLOXYPIPERIDINE-1-CARBOXYLATE and cesium fluoride were added in the above quantities to the reaction mixture. Heating was continued at 85C for a further 6 hours after the final addition. The solvent was evaporated, and the residue was partitioned between DCM (150 ml) and H20 (150 ml). The aqueous layer was extracted with DCM (4x 100 ml), and the extractions combined with the DCM layer. The combined DCM fractions were dried over MGS04 and evaporated. The residue was purified by chromatography, eluting with 0 to 2.5% (7: 1 MEOH/CONCENTRATED aqueous NH40H) in DCM. The appropriate fractions were combined and evaporated, giving the product as a light brown foam (2.40 g, 58%, allowing for 2.3 equivalents of residual DMA); HNMR : 1.40 (s, 9H), 1.60-1. 65 (m, 2H), 1.95-2. 00 (m, 2H), 3.20-3. 25 (m, 2H), 3.65-3. 70 (m, 2H), 3.92 (s, 3H), 4.68 (m, 1H), 7.21 (s, 1H), 7.27 (dd, 1H), 7.47 (ddd, 1H), 7.51 (dd, 1H), 7.85 (s, 1H), 8.36 (s, 1H), 9.53 (s, 1H) ; Mass Spectrum: 503.5, 505.5.
58% With cesium fluoride; In N,N-dimethyl acetamide; at 85℃; for 12h; Reference Example 3; 6-[(1-tert-Butoxycarbonyl) piperidin-4-yl] oxy}-4-(3-chloro-2-fluoroanilino)-7- methoxyquinazoline; 4- (3-Chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (Reference Example 2,1870 mg, 5.85 mmol) was dissolved in DMA (50 ml). tert-Butyl (4- methanesulfonyloxy) piperidine-l-carboxylate (prepared as in Chemical & Pharmaceutical Bulletin 2001,49 (7), 822-829; 490 mg, 1.76 mmol) and cesium fluoride (890 mg, 5.85 mmol) were added, and the mixture was heated to 85C with stirring. At intervals of 2 hours, 4 hours and 6 hours, tert-butyl 4-methanesulfonyloxypiperidine-1-carboxylate and cesium fluoride were added in the above quantities to the reaction mixture. Heating was continued at 85C for a further 6 hours after the final addition. The solvent was evaporated, and the residue was partitioned between DCM (150 ml) and H20 (150 ml). The aqueous layer was extracted with DCM (4x 100 ml), and the extractions combined with the DCM layer. The combined DCM fractions were dried over MgS04 and evaporated. The residue was purified by chromatography, eluting with 0 to 2.5% (7: 1 MeOH/concentrated aqueous NH40H) in DCM. The appropriate fractions were combined and evaporated, giving the product as a light brown foam (2.40 g, 58%, allowing for 2.3 equivalents of residual DMA) ; 1H NMR : 1.40 (s, 9H), 1.60-1. 65 (m, 2H), 1.95-2. 00 (m, 2H), 3.20-3. 25 (m, 2H), 3.65-3. 70 (m, 2H), 3.92 (s, 3H), 4. 68 (m, 1H), 7.21 (s, 1H), 7.27 (dd, 1H), 7.47 (ddd, 1H), 7.51 (dd, 1H), 7.85 (s, 1H), 8.36 (s, 1H), 9.53 (s, 1H) ; Mass Spectrum : 503.5, 505.5

 

Historical Records