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CAS No. : | 886372-63-0 | MDL No. : | MFCD07374960 |
Formula : | C6H7FN2O | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | CVMLVBYTEYUXOJ-UHFFFAOYSA-N |
M.W : | 142.13 | Pubchem ID : | 45480351 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
STEP 3: 4-(5-FLUORO^-(S-FLUORO-O-METHOXYPYRIDrN-S-YLAMrNO)PYRIDrN-S- YL)-6-METHYL- 1, 3, 5-TRIAZIN-2 -AMINE[00528] A solution of 4-(2-chloro-5-fluoropyridin-3-yl)-6-methyl-l,3,5-triazin-2-amine (100 mg, 0.417 mmol) and <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (120 mg, 0.844 mmol) (Anichem, NJ, USA) in THF (2.0 mL) was cooled in an ice bath under nitrogen. A THF solution of LiHMDS (1 M in THF, 2500 muL, 2.500 mmol) was added dropwise. After 5 min, the cooling bath was removed. After a total of 22 min, HCl (5 N, 0.5 mL) was added. After 5 min, EtOAc (10 mL) and saturated NH4Cl (10 mL) were added. The organic layer was washed with water (2 x 5 mL). The combined aqueous layers were extracted with EtOAc (2 x 5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was suspended in MeOH (5 mL) and filtered. The solid was washed with MeOH (2 x 2 mL), DCM (3 x 3 mL) and EtOAc (3 x 3 mL) to give the first batch of product as a brown solid. The combined washings were concentrated and purified on silica using 0-3% MeOH in DCM. The dark blue fraction contained the desired product (m/z 346) as a second batch. The combined product batches was suspended in ether (4 mL) and filtered to give the final product as a green solid (60 mg). LCMS (ES, pos.): calcd for Ci5H13F2N7O: 345.1; found: 346.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) delta 11.78 (s, 1 H); 8.56 (dd, J=9.78, 2.93 Hz, 1 H); 8.38 (br. s., 2 H); 8.28 (dd, J=12.81, 1.86 Hz, 1 H); 7.97 (br. s., 1 H); 7.84 (br. s., 1 H); 3.93 (s, 3 H); 2.44 (s, 3 H). 19F NMR (377 MHz, d6-DMSO) delta -140.84 (s, 1 F); -139.70 (s, 1 F). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
STEP 3 : 4-(5-CHLORO-2-(5-FLUORO-6-METHOXYPYRIDIN-3 -YLAMINO)PYRIDIN-3 - YL)-N-(2-METHOXYETHYL)-6-METHYL- 1 ,3,5-TRIAZIN-2 -AMINE[00535] A mixture of <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (Anichem, NJ, USA, 100 mg, 0.704 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-N-(2-methoxyethyl)-6-methyl-l,3,5-triazin- 2-amine (130 mg, 0.437 mmol) in THF (5 mL) was cooled in an ice bath and LiHMDS (1.0 M, 1500 muL, 1.500 mmol) was added under nitrogen. After 5 min, the cooling bath was removed. After 10 min, the mixture was neutralized with HCl (5 N, 0.3 mL) and then partitioned between EtOAc (20 mL) and water (10 mL). The organic layer was washed with water (5 mL). The combined aqueous layers were extracted with EtOAc (2 x 5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The resulting solid was triturated with EtOAc (5 mL) and filtered. The yellow solid was rinsed with ether (2 x 3 mL) to give the desired product as a yellow powder (115 mg). LCMS (ES, pos.): calcd for Ci8Hi9ClFN7O2: 419.1; found: 420.2 (M+H)+. 1H NMR (400 MHz, d6-DMSO) mixture of rotamers delta 11.89, 11.67 (s, 1 H); 8.73 (dd, J=6.75, 2.64 Hz, 1 H); 8.14 - 8.58 (m, 4 H); 3.94 (2s, 3 H); 3.46 - 3.65 (m, 4 H); 3.23, 3.29 (s, 3 H); 2.46, 2.47 (s, 3 H). 19F NMR (377 MHz, d6-DMSO) delta -139.65 (s); 139.26 (s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; | EXAMPLE 246. 4-(2-(5-FLUORO-O-METHOXYPYRIDIN-S-YLAMINO)PYRIDIN-S-YL)- 6-METHYL-l,3,5-TRIAZIN-2-AMINESTEP 1 : 4-(2-(5-FLUORO-O-METHOXYPYRIDIN-S-YLAMINO)PYRIDIN-S-YL)-N1N- BIS(4-METHOXYBENZYL)-6-METHYL-l,3,5-TRIAZIN-2-AMINE[00637] A solution of THF (3 mL) containing <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (87 mg, 0.613 mmol) (Anichem) and 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6- methyl-l,3,5-triazin-2-amine (Example 52; 182 mg, 0.409 mmol) was cooled to 0 0C in an ice bath and treated dropwise with 1 M LiHMDS (1.226 mL, 1.226 mmol). The solution was stirred at this temperature for 1.5 h and quenched with a saturated solution OfNH4Cl. The product was extracted with EtOAc (15 mL), dried over MgSO4, filtered and concentrated to give crude 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4- methoxybenzyl)-6-methyl-l,3,5-triazin-2-amine (269.7 mg, 0.475 mmol) as a bright yellow amorphous solid which was used in the next step without further purification, m/z (ESI, +ve ion) 568.0 (M+H)+. 1H NMR (400 MHz, CDCl3) delta 11.94 (1 H, s); 8.82 (1 H, dd, J=7.8, 2.0 Hz); 8.29 (1 H, dd, J=4.8, 2.1 Hz); 8.05 (1 H, dd, J=12.3, 2.2 Hz); 7.97 (1 H, d, J=2.3 Hz); 7.20 (4 H, dd, J=10.6, 8.6 Hz); 6.86 (4 H, t, J=9.0 Hz); 6.78 (1 H, dd, J=7.8, 4.7 Hz); 4.84 (2 H, br. s.); 4.83 (2 H, br. s.); 4.01 (3 H, s); 3.81 (3 H, s); 3.79 (3 H, s); 2.58 (3 H, s). | |
With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; for 1.75h; | LiHMDS (1M in THF, 0.694 mL, 0.694 mmol) was added (dropwise) to a solution of <strong>[886372-63-0]5-fluoro-6-methoxypyridin-3-amine</strong> (27, 49.3 mg, 0.347mmol; Anichem, Inc.,North Brunswick, NJ) and4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine2(2a; 103 mg, 0.231 mmol) in THF (3 mL) at 0 C, and the resulting mixture was stirred at 0 C for 105 min. The reaction mixture was then quenched (at 0 C) with saturated aqueous NH4Cl solution and extracted with EtOAc (15 mL). The organic extract was dried over MgSO4, filtered, and concentrated in vacuo to provide 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (146 mg, 0.257 mmol, >99% yield) as a bright-yellow solid, which was used without further purification. |
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