2-bromobenzo[d]thiazole-6-carbonitrile

A cooled solution of crude {2-[4-(2-hydroxyethyl)piperidin-l-yl]pyrimidin-5-yl}boronic acid (intermediate 5), formed as described above, was diluted with dioxane (3 ml), and 6-cyano- 2-bromobenzothiazole (229 mg, 1 eq) was added followed by bubbling of N2 for 1 min. Then 2 M K2CO3 (1.4 ml, 3 eq) was added followed by Pd(dppf)C DCM complex 1:1 (40 mg, 5 mol%). The solution was again bubbled with N2 for 5 min then the vial was capped. The reaction was run in a preheated oil bath at 90 C overnight. The reaction mixture was cooled, diluted with ethyl acetate and the solid filtered. The solid was refluxed with ethyl acetate, and then ethanol was added. The crude solid product was filtered hot. The solid that was filtered off (250 mg of crude product) was retained for use as the crude 2-{2-[4-(2-hydroxyethyl)piperidin-l-yl]pyrimidin-5-yl}-l, 3-benzothiazole-6- carbonitrile starting material in the synthesis of Example Compound 41. The filtrate was allowed to cool and the solid was filtered to give the 2-{2-[4-(2-hydroxyethyl)piperidin-l- yl]pyrimidin-5-yl}-l, 3-benzothiazole-6-carbonitrile (19 mg solid, HPLC Rf 3.11, MS m/z (M+l) 366.0). TLC: ethyl acetate Rf 0.33.To a solution of (1R, 5S)-7-((5-cyclopropyl-3-(2, 6-dichlorophenyl)isoxazol-4-yl)methoxy)-3-oxabicyclo[3.3.1]nonan-9-one (2f, 120 mg, 0.28 mmol) and 2-bromo-benzo[d]thiazole-6-carbonitrile (70 mg, 0.28 mmol) in dry THF (20 mL) was cooled to -78 C., n-BuLi (0.28 mmol, 1.6M) was added dropwise. The mixture was stirred at -78 C. for 2 h and then quenched with sat. NH4Cl (30 mL) and extracted with EtOAc (3*50 mL). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, concentrated and purified by silica-gel column chromatography (DCM/MeOH=30:1) to give 2-((1R, 5S, 9S)-7-((5-cyclopropyl-3-(2, 6-dichlorophenyl)isoxazol-4-yl)methoxy)-9-hydroxy-3-oxabicyclo[3.3.1]nonan-9-yl)benzo[d]thiazole-6-carbonitrile.General procedure: j00728j A mixture of aryl halide (1-2 eq.), compound A-2 (racemic or a single enantiomer, 1 eq.), palladium complex (0.05-0.10 eq.), ligand (0.05-0.10 eq), and base (1-2 eq.) in dioxane (5-10 mL/mmol) under nitrogen was heated with stirring at the indicated temperature for the indicated time. On completion, the mixture was filtered and concentrated under vacuum. The residue was purified byprep HPLC or silica gel chromatography, and mixtures of enantiomers were separated by chiral SFC. Most compounds were treated with 0.2 M hydrochloric acid and lyophilized to give hydrochloride salts.Following general procedure 1C, beginning with intermediate 4-((5-cyclopropyl-3-(spiro[2.5]octan- 6-yl)isoxazol-4-yl)methoxy)cyclohexanone (lnt-4-2) and 2-bromobenzo[ /|thiazole-6-carbonitrile, the title compound 2-((1 s, 4s)-4-((5-cyclopropyl-3-(spiro[2.5]octan-6-yl)isoxazol-4-yl)methoxy)-1 - hydroxycyclohexyl)benzo[

Molecular Weight:239.09
XLogP3:3.3
Hydrogen Bond Acceptor Count:3
Exact Mass:237.92003
Monoisotopic Mass:237.92003
Topological Polar Surface Area:64.9
Heavy Atom Count:12
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes