5-Bromo-2-benzothiazolamine

solid

General procedure: To a solution of the commercially available aniline (1.0 eq) in acetic acid (0.5 M), was added ammonium thiocyanate (5.0 eq) at rt. After 90 min, the thick suspension was cooled to 0°C, and bromine (1.1 eq) in acetic acid (1.0 M) was added. After 1 h, the reaction was allowed to warm to rt. After a subsequent 1 h, the mixture wasconcentrated to remove acetic acid. A small amount of water was added, then the mixture was adjusted to pH 12 with concentrated ammonium hydroxide. The resulting mixture was extracted with EtOAc (x3) and the combined organics were washed withNaHC03(To a solution of 2, 5-dibromo-phenyl)-thiourea III (2.0 g, 6.5 mmol) in N- methylpyrrolidone (10 mL) was added NaH (60percent dispersion in mineral oil, 0.24 g, 9.70 mmol) at room temperature. The reaction mixture was heated up to 160General procedure: N-Silylated amines 6a's were prepared by reaction of the requisite heteroaromatic amine precursor in neat TMSCN (1 mL of TMSCN permmol of the amine) with stirring under N2 at 70 °C. The N-silylation times for each amine are shown in Table 1. The excess TMSCN was removed under high vacuum and the derived N-silylated amine was used without purification in the amidation reaction. The percent conversion of each amine into its N-silylated derivative was determined by 1HNMR spectroscopy (CD3CN; passed through a basic alumina column prior to use).To a suspension of intermediate 1 (0.35 g, 1.3 mmol) in DCE (4 mL) was added SOCb (0.925 mL, 12.7 mmol) and the reaction mixture was heated to 50 °C. The reaction turned clear and was stirred for lh. The solvents were removed under reduced pressure and to the resultant solid was added 5-bromobenzo[ithiazol-2-amine (0.32 g, 1.4 mmol), THF (3 mL) and DIEA (0.66 mL, 3.8 mmol). After 24 h, the solvents were evaporated under reduced pressure and the residue was purified via silica gel (0605) chromatography eluting with DCM/0-100percent ethyl acetate to afford (0.385 g, 62.9 percent yield) of N-(5-bromobenzo[d]thiazol-2-yl)-2-(4-((3-cyanopyridin-2-yl)oxy)-3- fluorophenyl)acetamide as a yellow solid. NMR (400 MHz, CDCb) delta 9.06 (br s, IH), 8.34 (dd, J=4.8, 2.0 Hz, IH), 8.07 (dd, 7=7.7, 2.0 Hz, IH), 7.93 (d, 7=1.8 Hz, IH), 7.72 (d, 7=8.6 Hz, IH), 7.55 - 7.46 (m, IH), 7.51 - 7.45 (m, IH), 7.36 (t, 7=8.0 Hz, IH), 7.28 - 7.14 (m, 2H), 3.92 (s, 2H). LCMS m/z = 484.9 (M+H).+

Molecular Weight:229.10
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:227.93568
Monoisotopic Mass:227.93568
Topological Polar Surface Area:67.2
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes