* 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.
With n-butyllithium; diisopropylamine; In tetrahydrofuran; at -78℃; for 1h;Inert atmosphere;
[0123] To diisopropylamine (1.028 ml, 7.21 mmol, 1.8 equiv) in 10 mL THF at 0 C was added n-butyl lithium (3.76 ml, 6.01 mmol, 1.5 equiv). After 1 h, the LDA solution was transferred to a solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (1.0 g, 4.01 mmol, 1.0 equiv) in 35 mL THF at -78 C under nitrogen. The solution stirred for 1 h at -78 C after which a mixture of 1.25 mL water and 5 mL THF was added slowly. The mixture was then warmed to 0 C, poured into 60 mL water, and extracted with dichloromethane. The combined organic extracts were then dried over Na2SC> , filtered, and concentrated in vacuo to give a yellow solid which was chromatographed with 20% EtOAc/Hexanes gradient elution to give 5-bromo-4-chlorothieno[2,3-d]pyrimidine (671 mg, 67.1 % yield) as a tan solid. NMR (400 MHz, chloroform- ) delta ppm 8.85 (s, 1 H), 7.64 (s, 1 H).
56%
With lithium diisopropyl amide; In tetrahydrofuran; n-heptane; ethylbenzene; at -78℃; for 1h;Inert atmosphere;
Step 4: To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (3 g, 12.048 mmol) in THF (120 mL) was added 2M LDA solution in THF/heptane/ethylbenzene (9 mL, 18.072 mmol) at -78 C under nitrogen. The reaction mixture was stirred for 1 h at -78 C, a mixture of 3.75 mL water and 15 mL THF was added slowly. The mixture was warmed to 0 C, poured onto water (180 mL). The reaction mixture was extracted with dichloromethane (2 x 50 mL). The combined organic extracts were dried over Na2S04, filtered, and concentrated in vacuo to give crude product. The crude product was purified by flash column chromatography with 80 g silica column and 10% EtOAc in Hexanes as eluent to give 5-bromo-4-chlorothieno[2,3- cdpyrimidine as yellow solid (1.7 g, 56%). LCMS (ES) m/z = 248.9, 250.9 [M+H]+. H NMR (400 MHz, CDCI3) delta ppm 7.66 (s, 1 H), 8.87 (s, 1 H).
55%
Lithium diisopropylamine (LDA) was prepared by addition of 2.5 molar BuLi (3.0 mL, 7.6 mmol) in hexanes to a ca. -50 C. solution of diisopropylamine (1.1 mL, 790 mg, 7.8 mmol) in anhydrous THF (15 mL). The solution was warmed to 0 C. for 10 min and then added dropwise to a solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (which was prepared as disclosed in WO 2003053446) (2.0 g, 8.0 mmol) in THF (30 mL) cooled to -100 C. The mixture was maintained at -90 to -100 C. for 45 minutes and then quenched with saturated aqueous NH4Cl. The mixture was diluted with ethyl acetate (30 mL) and the separated organic phase was washed with water, brine, dried (Na2SO4) and evaporated. The residue was recrystallized from aqueous ethanol and the isolated solid was dissolved in dichloromethane and passed through a silica gel plug eluting with dichloromethane to yield 900 mg of material. A further 200 mg of product was obtained from the evaporated, recrystallization filtrate by reverse phase High Pressure Liquid Chromatography (HPLC) on a 50 mm×250 mm YMC-AQ eluting with 70/30 acetonitrile/0.1 percent v/v water-conc. H2PO4. Total yield was 1.1 g (55 percent). In later runs the crude bromide was recrystallized from acetonitrile.
46%
With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; for 1h;Inert atmosphere;
To a stirred solution of 6-bromo-4-chlorothieno[2,3-c]pyrimidine (1 g, 4.0 mmol, 1 equiv) in THF (40 mL) was added 2M LDA in THF solution (3 mL, 6.0 mmol, 1.5 equiv) drop wise at -78 C under nitrogen. The reaction was stirred for 1 h at -78 C after which a mixture of water (1.25 mL) and THF (5 mL) was added slowly. The mixture was then warmed to 0 C, poured onto water (60 mL), and extracted with DCM (2 x 30 mL). The combined organic extracts were combined and dried over Na2S04, filtered and concentrated. Purification: Purified by flash column chromatography, 24g silica column with 10% EtOAc in hexane as mobile phase to give 5-bromo-4-chlorothieno[2,3-c]pyrimidine as yellow solid. Yield (0.46 g, 46 %). LC-MS (ES) m/z = 248.9 [M+H]+. H NMR (400 MHz, CDCI3) delta 7.66 (s, 1 H), 8.87 (s, 1 H).
A stirred solution of <strong>[56844-12-3]6-bromo-4-chlorothieno[2,3-d]pyrimidine</strong> (4.0g, 0.016mol) in anhydrous tetrahydrofuran (100ml) was cooled in a dry-ice/acetone bath and treated, under a nitrogen atmosphere, with lithium diisopropylamide (1.8M solution in tetrahydrofuran, 9.0ml, 0.016mol) over about 20 minutes. The resultant dark solution was stirred in the cold for 1 hour and then treated with a mixture of water (5ml) and tetrahydrofuran (20ml) over about 20 minutes. The mixture was then allowed to warm up to about 0C before being poured into water (250ml) and extracted with dichloromethane (SxlOOml). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo to give the crude product. Purification by flashchromatography (silica) eluting with dichloromethane gave 5-bromo-4-chlorothieno[2,3-cQpyrimidine as a pale brown solid (3.8g).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
