2-Bromo-4-methylthiazole

Clear light red liquid

100 g (0, 56 mol) 2-Brom-4-methylthiazol werden in 106 ml wasserfreiem Dimethylformamid gelost und die Mischung bei Raumtemperatur in einen HC-Autoklaven eingetragen. Nun werden 213, 28 g (2, 25 mol) Brommethan aufgepresst, so das der Druck auf 1, 9 bar ansteigt. Anschliessend wird das Reaktionsgemisch bei guter Durchmischung mit einer Heizrate von 8C/Minute auf 70C erwarmt und die Temperatur solange isobar gehalten, bis die Umsetzung moglichst quantitativ ist. Die Umsetzung wird dabei massenspektroskopisch verfolgt. Zur Aufarbeitung kuhlt man auf Raumtemperatur, entspannt den Autoklaven und filtriert das Produkt ab. Losungsmittelreste und Verunreinigungen werden durch Waschen mit 300 ml Hexan entfernt und das Produkt im Hochvakuum getrocknet. Ausbeute: 107, 5 g (70 % d. Theorie)Example II-A At 10 C., 11.6 mol of hydrogen bromide were passed with the exclusion of moisture into a solution of 280 g (2.30 mol) of thiocyanatopropan-2-one in 4, 500 ml of dichloromethane such that a temperature of 10 C. was not exceeded. Hydrogen bromide was generated from bromine and tetralin in the course of this reaction according to processes known from the literature. In a modification of the literature procedure, the addition of catalytic amounts of iron was dispensed with and the reaction temperature for the generation of hydrogen bromide was increased to 40 C. After the addition of the hydrogen bromide was complete (about 6 h), the mixture was stirred at room temperature for 12 h. The product obtained as the hydrobromide was filtered off with suction, washed with 1, 500 ml of dichloromethane, and again suspended in 3, 000 ml of dichloromethane. 2, 500 ml of saturated sodium hydrogen carbonate solution were then added in a 20 liter glass reactor at 0 C. with vigorous mixing (9 600 min-1) such that a temperature of 5 C. was not exceeded. The organic phase was separated off, dried over MgSO4, and the solvent was distilled off at 30 C. and 50 mbar on a rotary evaporator. The residue that remained was then fractionally distilled. Yield of To a stirred solution of 19B. methyl 3-(3-((4-chlorophenyl)amino)-4-(4-methylthiazol-2-yl)phenyl)pentanoate (Absolute Stereochemistry not Determined) 19A (20 mg, 0.047 mmol), potassium phosphate tribasic (19.76 mg, 0.093 mmol) and The compound 7-1 (100 mg, 0.25 mmol) was dissolved in 1, 4-dioxane (3 mL), and added with To a solution of compound G1 (3 g, 16.8 mmol) , compound G2 (4.5 g, 20.2 mmol) , tetrakis (triphenylphosphine) palladium (0) (1.96 g, 1.7 mmol) in 1, 4-dioxane (120 mL) was added potassium acetate (3.3 g, 33.6 mmol) and the reaction was stirred at 100 for 16 hours under nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water (100 mL) , extracted with EtOAc (100 mL × 3) . The organic layers were washed with brine (100 mL) , dried over anhydrous Na 2SO 4 and concentrated under vacuum to afford crude product, which was purified by silica gel chromatography (elution gradient: DCM/MeOH, 8/1, v/v) . Pure fractions were evaporated to dryness to afford compound G3 (1.6 g) as a brown oil, yield: 40.8%. LCMS: Rt = 0.64 min, MS Calcd.: 194.1, MS Found: 194.9 [M+H] +.

Molecular Weight:178.05
XLogP3:2.4
Hydrogen Bond Acceptor Count:2
Exact Mass:176.92478
Monoisotopic Mass:176.92478
Topological Polar Surface Area:41.1
Heavy Atom Count:7
Complexity:68.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes