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CAS No. : | 26456-59-7 | MDL No. : | MFCD06412562 |
Formula : | C4H4N2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LTXJLQINBYSQFU-UHFFFAOYSA-N |
M.W : | 96.09 | Pubchem ID : | 565855 |
Synonyms : |
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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 |
---|---|---|
With caesium carbonate;2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 130℃;Sealed tube; | 5-(2,5-Dimethyl-4-nitrophenoxy)pyrimidine; A solution of l-bromo-2,5-dimethyl-4-nitrobenzene (3.53 g, 15.34 mmol), pyrimidin-5-ol (1.474 g, 15.34 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (0.141 g, 0.767 mmol), cesium carbonate (5.15 g, 15.80 mmol) and copper(I) chloride (0.410 g, 4.14 mmol) in N-methyl-2-pyrrolidinone (15.34 mL) was heated in a sealed pressure tube at 130 C and stirred overnight. The reaction was cooled to room temperature, diluted with EtOAc and washed with water (2x) and brine, successively, dried over Na2SO4, filtered and concentrated in vacuo. This was triturated with diethyl ether to give the first crop of the desired product (1.682 g) as a light tan solid. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography using an ISCO 80g column eluting with 0-50%EtOAc/hexanes. Appropriate fractions were collected and concentrated in vacuo to give the second crop of the desired product (0.3973 g) as an off- white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.1% | With potassium carbonate; In N,N-dimethyl-formamide; at 25 - 80℃; for 36h;Large scale; | To a solution of 5-hydroxypyrimidine (9, 1.73 kg, 18.08 mol) in DMF (23.0 L,10 V), potassium carbonate (6.25 kg, 45.21 mol) was added followed by <strong>[104711-65-1]4-chloro-6-methylpicolinonitrile</strong> (8, 2.3 kg, 15.07 mol) at 25-30 C. The reactionmass was heated at 75-80 C for 36 h. The reaction was monitored by HPLC 8NMT 2.0% by HPLC). Reaction mass was cooled to 25-30 C. The solid wasfiltered and washed the solid with DMF (4.6 L, 2.0 V). The filtrate was cooled to0-5 C and purified water (27.6 L, 12 V) was added drop wise over a period of1 h. The solid precipitated was filtered and washed with purified water (2.3 L,10 V) to afford 10 as off white solid (2.62 kg, 82.1%). 1H NMR (400 MHz, DMSOd6)d 9.17 (s, 1H), 8.85 (s, 2H), 7.74 (d, J = 2.4 Hz, 1H), 7.32 (d, J = 2.3 Hz, 1H),2.48 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d = 164.04, 162.28, 155.51, 150.02,148.75, 133.54, 117.05, 115.59, 115.04, 23.82 ppm; LCMS (Method 1):RT = 0.535 min, m/z = 213.2 [M+H]+; HRMS, calc?d for C11H8N4O [M],212.0698; found 212.0697. |
77% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h; | d. PREPARATION OF 6-METHYL-4-(PYRIMIDIN-5-YLOXY)PICOLINONITRILE.[00399] <strong>[104711-65-1]4-chloro-6-methylpicolinonitrile</strong> (4.0 g, 26 mmol, 1.0 eq), 5-hydroxypyrimidine (5.56 g, 57.9 mmol, 2.20 eq), K2C03 (7.24 mg, 52.4 mmol, 2.0 eq) and DMF (66 mL) were added to a reaction vessel and heated at 80 C for 16 hours. The reaction was filtered and concentrated on silica gel (25 g). The silica gel was loaded on top of a fresh bed of silica gel and washed with 50% ethyl acetate/hexane. The solvents were removed in vacuo and the crude solid was purified by flash chromatography on silica gel to afford 4.31 g (77%) of the title compound as a pale-yellow solid. NMR (400 MHz, DMSO-) delta 9.1 7 (s, 1 H), 8.85 (s, 2H), 7.74 (d, J = 2.4 Hz, 1 H), 7.32 (d, J = 2.3 Hz, 1 H), 2.48 (s, 3H); ES-MS [M+l ]+: 213.2. |