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With hydrogen iodide; sodium iodide; In water; at 70℃; for 0.5h;
Description 93; 6-IodoPvrimidin-4-amine-?,; A mixture of 4-amino-6-chloropyrimidine [WO-A-0245652] (1. 00 g, 7.72 mmol), sodium iodide (5.79 g, 38.6 mmol) and 40% HI (20 ml) were heated at 70C for 30 min, then allowed to cool to room temperature. The precipitate was removed by filtration, and partitioned between dichloromethane and sat. NaHCO3. The organic layer was separated, and dried over Na2SO4, filtered, and evaporated to give the title compound (1.2 g, 70%). 1H NMR (400 MHz, DMSO-d6) 6.89 (1 H, s), 7.04 (2 H, br s), 8.04 (1 H, s).
65%
With hydrogen iodide; In water; at 0 - 20℃; for 18.5h;
6-Chloropyrimidin-4-ylamine (450 mg) was added in portions to HI (57% wt. aq. , 20 mL) at 0 C. The reaction mixture was stirred for 30 minutes at 0 C and then at ambient temperature for 18 hours. The reaction mixture was treated with NaHC03 (sat. aq. ) until pH8 was achieved and then the product extracted with EtOAc (2 x 30 mL). The combined organics were washed with NaOH (2M, aq. ), dried (MgS04), filtered and then concentrated. The crude product was used directly without further purification (500 mg, 65%); lH NMR (CDCl3) ; 6.90 (s, 1H), 7.03 (s, 2H), 8.05 (s, 1H); MS m/e MHs 221.
47%
With hydrogen iodide; In water; at 0 - 20℃; for 3.0h;
General procedure: 2-Amino-4-chloropyrimidine (55) (13.0g, 100mmol) was added to a 57wt.% aqueous solution of hydriodic acid (115ml, 1.00mol) at 0C and the mixture was stirred at room temperature for 3h. The mixture was cooled to 0C and the resulting precipitate was removed by filtration and taken up in cold 5N aqueous Na2CO3 (200ml). The mixture was extracted with EtOAc (3×500ml) and the combined organic layers were concentrated under reduced pressure to deliver 2-amino-4-iodopyrimidine (21.1g, 95.0mmol, 95% yield) as a white solid.
In 1,3-dimethyl-2-imidazolidinone; at 130℃; for 6.5h;
A solution of 6-amino-4-chloropyrimidine (1) (0.504 g, 3.89 mmol) and N- <strong>[6092-47-3]chloroacetylurethane</strong> (0.770 g, 4.65 mmol) in 1, 3-dimethyl-2-imidazolidinone (10 mL) was heated to 130C under nitrogen for 3 h. N-Chloroacetylurethane (0.770 g, 4.65 mmol) was added and the mixture was heated to 130C under nitrogen for a further 3.5 h. The black oily solution was poured onto ice (200 g) and the aqueous solution was extracted with ethyl acetate (3 x 250 mL). The organic fractions were combined, removal of solvent in vacuo gave an oily solid which was triturated with ether. Filtration of the solid and washing with ether gave urethane (2) (88 mg, 9%) as a solid. APCI-MS Found [M + H] + = 241,243.
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Microwave irradiation;
Step A: 2'-methoxy-4,5'-bipyrimidin-6-amine6-Chloropyrimidin-4-amine (0.35 g, 2.70 mmol), 2-methoxypyrimidin-5- ylboronic acid (0.520 g, 3.38 mmol), Na2C03 (0.859 g, 8.11 mmol) andbis(triphenylphosphine)palladium(II) chloride (0.038 g, 0.054 mmol) were suspended in a mixture of DME/EtOH/water. (15:2:3 mL). The mixture was heated in the microwave synthesizer at 125 °C for 20 min and concentrated. The residue was purified by silica gel chromatography (0-5 percent 9: 1 methanol: ammonium hydroxide- ethyl acetate) to afford 6-(pyridin-3-yl)pyrimidin-4-amine (0.28 g, 1.378 mmol, 51 percent yield) as an off-white solid. LCMS R.T. = 0.53; [M+H]+ = 204.11.
51%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 125℃; for 0.333333h;Microwave irradiation;
6-Chloropyrimidin-4-amine (0.35 g, 2.70 mmol),<strong>[628692-15-9]2-methoxypyrimidin-5-ylboronic acid</strong> (0.520 g, 3.38 mmol),Na2CO3 (0.859 g, 8.11 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.038 g, 0.054 mmol) were suspendedin a mixture of DME/EtOH/water. (15:2:3 mL). Themixture was heated in the microwave synthesizer at 125° C.for 20 min and concentrated. The residue was purified bysilica gel chromatography (0-5percent 9:1 methanol:ammoniumhydroxide-ethyl acetate) to afford 6-(pyridin-3-yl)pyrimidin4-amine (0.28 g, 1.378 mmol, 51percent yield) as an off-white solid.
With sodium hydride; In N,N-dimethyl-formamide; oil; at 0 - 70℃; for 23.1667h;
Step 1-Synthesis of 6-(6-iodoindazol-1-yl)pyrimidin-4-amine To a solution of <strong>[261953-36-0]6-iodoindazole</strong> (500 mg, 2.05 mmol) in DMF (8 mL) was added NaH (60% oil dispersion, 131.12 mg, 3.28 mmol) at 0 C. The mixture was stirred at 0 C. to RT for 10 minutes before addition of 6-chloropyrimidin-4-amine (477.78 mg, 3.69 mmol) and stirring at 60 C. for 17 hr and then transferred to a pressure tube and heated at 70 C. for a further 6 hr. The reaction mixture was cooled and quenched by the addition of water (10 ml) and EtOAc (a few drops) was added. The resultant precipitate was collected by suction filtration and then thoroughly dried under high vacuum to give the title intermediate (248 mg): LC-MS: m/z=+338.20 (M+H)+.
2-(1-(6-aminopyrimidin-4-yl)-1H-imidazole-4-yl)ethan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
58%
With caesium carbonate; In N,N-dimethyl-formamide; at 140℃; for 12h;
A solution of 1.12 g (10 mmol) of 2- (1 H-imidazol-4-yl) ethan-1-ol was dissolved in 20 ml of DMF, 1.30 g of (lOmmol) of 4-amino-6-chloroetine, g (12 mmol) of cesium carbonate, the temperature was raised to 140 C and the reaction was stirred for 12 h. And the residue was purified by silica gel column chromatography. The eluent was methanol: dichloromethane = 1: 30 to give 1.19 g of the compound as shown on the white solid (yield of the compound of the formula IIb-1) in a yield of 58%.
58%
With caesium carbonate; In N,N-dimethyl-formamide; at 140℃; for 12h;
General procedure: A mixture of imidazole derivatives (4a-c, 10mmol), 4-amino-6-chloropyrimidine (1.30g, 10mmol), and K2CO3 (2.07g, 15mmol, for 5a) or Cs2CO3 (3.91g, 12mmol, for 5b-c) was stirred in DMF (20mL) at 100C (for 5a) or at 140C (for 5b-c) for 12h. Water (100mL) was then added. The mixture was extracted with EtOAc (3×50mL). The organic layer was separated and dried over Na2SO4. Removal of the solvents produced a residue which was purified using column chromatography and eluted with a mixture of MeOH:CH2Cl2 (1:30, v:v) to afford 5a-c.
General procedure: 4-amino-6-chloropyrimidine (200 mg, 1.54 mmol) and KI(127.82 mg, 0.77 mmol) was dissolved in ethanol (35 mL). Trifluoroaceticacid (200 mL) was added after stirring and heating10 min for activating pyrimidine. Then to a stirred solution ofsubstituted aniline (1.23 mmol) in ethanol (15 mL) was added byway of drip for 1 h. The resulting mixture was heated to reflux for36 h, allowed to cool to room temperature, and concentrated invacuo. Then the solid residue was diluted with ethyl acetate and asaturated aqueous solution of NaHCO3. The aqueous layer wasseparated and extracted with ethyl acetate. The organic phase waswashed with brine, dried (Na2SO4), filtered, and concentrated. Purificationof the crude product by silica gel column chromatography(ethyl acetate/light petroleum, 2:1 and 1:1), provided the desiredproduct (batch1). Substituted aniline (2,6-dichloro and 3,5-dimethoxy) (200 mg) was dissolved in CH2Cl2 (15 mL) was addedby way of drip phosgene which dissolved in CH2Cl2 (20 mL)(batch1/phosgene, 2:1 (mol)) at 0 C for 0.5 h. The resulting mixturewas heated to reflux for 3e6 h, allowed to cool to room temperature,and concentrated in vacuo. Then the solid residue was dilutedwith ethyl acetate and a saturated aqueous solution of NaHCO3. Theaqueous layer was separated and extracted with ethyl acetate. Theorganic phase was washed with brine, dried (Na2SO4), filtered, andconcentrated. Purification of the crude product by silica gel columnchromatography (CH2Cl2/MeOH/aqueous NH3, 96:3:1), providedthe desired product (batch2). Batch1 and batch2 (batch1/batch2,5:6 (mol)) were dissolved in toluene (10 mL,18.89 mmol), theresulting mixture was heated to reflux for 8e10 h, allowed to coolto room temperature, then filtered by toluene to provide the endproduct(the residue).
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