3-Cyanobenzeneacetic acid

The amine B4 (19 mg, 116 pmol, 1.2 eq), HOBt (20 mg, 144 pmol, 1.5 eq), EDCI (28 mg, 144 pmol, 1.5 eq) and DIPEA (50 mg, 385 pmol, 67 pL, 4 eq) were dissolved in DMF (10 mL). 2-(3- Cyanophenyl)acetic acid (30 mg, 96 pmol, 1 eq) was added. The mixture was stirred at 25C under N2 for l2hrs. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was purified by preparative-HPLC (TFA condition: Column: UniSil 120 x 30 mm, 10 pm; mobile phase: [water (0.l%TFA)-ACN]; ACN%: 20%-50%, 11 min) which provided amide B5.General procedure: The amine compound and 1.1 equivalent phenylaceticacid were dissolved in ethylacetate (in case of solubilityproblems 20-50% dimethylformamide was also added). 1.2 equivalentcarbodiimide (dicyclohexylcarbodiimide or ethyldimethylaminopropylcarbodiimide) was added and stirred atambient temperature overnight. Dicyclohexylurea was removed byfiltration while ethyl-dimethylamino propylurea was removed byextraction with water and brine. The organic solvent was alsoextracted with sodium carbonate solution in both cases and theorganic phase was dried and evaporated. The crude products werepurified on silica column (eluent: ethylacetate or chloroformmethanol 10:1).To a mixture of compound 52-S1 (21 mg, 0.13 mmol) and (1R, 3S, 5R)-N-(6-bromo-3- methylpyridin-2-yl)-5-methyl-2-azabicyclo[3.1.0]hexane-3-carboxamide TFA salt (53 mg, 0.13 mmol) in DMF (2 mL) was added N-ethyldiisopropylamine (84 mg, 0.65 mmol) followed by HATU (76 mg, 0.2 mmol) at 0 oC, and the reaction was stirred at room temperature for 1 hour. The mixture was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with saturated aq. NH4Cl solution and brine, dried with anhydrous Na2SO4, and concentrated to dryness. The residue was purified by column chromatography on silica gel (eluted with PE: EtOAc= 2: 1) to give compound 52-S2 (45 mg, yield 76.3percent) as a yellow solid. LC/MS (ESI) m/z: 453 (M+H)+.General procedure: Compound 16 (216 mg, 1.0 mmol), phenylacetic acid (150 mg, 1.10 mmol) and N-(1-methanesulfonyl)benzotriazole (220 mg, 1.10 mmol) were placed in a microwave reaction vessel. TEtaF (2 mL) was added followed by Et3N (0.5 mL, 3.59 mmol) and the mixture heated in the sealed tube at 160 °C for 10 minutes. Upon cooling to RT the reaction was concentrated to l mL, and then MeCN was added (4mL) and the product 2-phenyl-N-[4-(1H-pyrrolo[2, 3-b]pyridin-3-yl)-thiazol-2-yl]-acetamide precipitated, was filtered, washed with acetonitrile and dried.

Molecular Weight:161.16
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:161.047678466
Monoisotopic Mass:161.047678466
Topological Polar Surface Area:61.1
Heavy Atom Count:12
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes