4-Bromomethylbenzamide

α-Bromo-p-toluic acid (8.00 g, 37.2 mmol) was stirred as a suspension in CClStirred the solution of 4-(bromomethyl)benzonitrile (1.5 g) in cocn.H2SO4 at 100°C for 3-4 h. After completion of the reaction, the reaction mass was quenched in ice and filteredto afford 0.900 of desired product. Example 45: l-(l-(4-carbamoylbenzyl)-5, 6-dimethyl-lH-benzo[d]imidazol-2-yl)-7V- cyclopentylpiperidine-4-carboxamideTo a solution of l-(l-(4-bromobenzyl)-5, 6-dimethyl-lH-benzo[d]imidazol-2-yl)-N- cyclopentylpiperidine-4-carboxamide (0.1 g, 0.29 mmol) in N, Lambda/-dimethylformamide (0.5 mL) was added caesium carbonate (0.566 g, 1.7 mmol), followed by (273 mg, 1.274 mmol) was added to a solution of methyl 3-0X0-3, 4-dihydro-2H-benzo[b][l, 4]oxazine-6-carboxylate (264 mg, 1.274 mmol) and cesium carbonate (415 mg, 1.274 mmol) in DMF (3 mL), and the reaction stirred overnight at 50 C. The reaction was diluted with ethyl acetate (10 mL) and washed with H20 (3 x 3 mL). The organic phases were combined, dried over Na2S04, filtered and concentrated to afford methyl 4- (4-carbamoylbenzyl)-3-oxo-3, 4-dihydro-2H-benzo[b][l, 4]oxazine-6-carboxylate (313.8 mg, 0.922 mmol, 72.4%) as a light brown solid which was used directly in the next step without further purification. MS: (ES, m/z): 340 [M+H]+.Compound 13 (1 eq.), benzyl bromides (1 eq.) and Cs2CO3 (1.1 eq.) were stirred overnight in acetonitrile. The mixture was diluted with ethyl acetate. The organic layer was washed with brine, dried with Na2SO4, concentrated and purified with sil gel chromatography (CH2Cl2: MeOH 25:1) to get the product.General procedure: To a solution of the isoflavone (4a-d) (0.18 mmol, 1.00equiv.) in acetone (5 mL), K2CO3 (1.8 mmol, 10.00 equiv.) was added. After stirring for 15 min the corresponding alkyl/benzyl bromide(0.9 mmol, 5.00 equiv.) was added drop wise to the mixture and stirred at 45 C overnight. After removing the acetone in vacuo, H2O(10 mL) and EtOAc (20 mL) were added and the aqueous phase was extracted with EtOAc (3 20 mL). The combined organic layers were dried over Na2SO4, and finally concentrated under reduced pressure. The residue was purified by FC using Petroleum Ether/EtOAc as eluent to give the corresponding substituted-isoflavone (5-19) (Supplementary Material).To a suspension of 4-ethyl-2-mercapto-6-(4-methyl-1, 4-diazepan-1-yl)pyridine-3, 5-dicarbonitrile (synthesis described in example 69, step 1, 60 mg, 0.199 mmol) and 4- (bromomethyl)benzamide (42 mg, 0.196 mmol) in N, N-dimethylformamide (1.0 mL) at room temperature was added triethylamine (0.055 mL, 0.398 mmol). The reaction mixture was then stirred at room temperature overnight. The reaction mixture was filtered and the filtrate was purified by reverse phase HPLC (Gilson, 30 mm x 50 mm Gemini Column, NH4OH modifier) to obtain the purified desired product. The isolated material was repurified by reverse phase HPLC (Gilson, 30 mm x 50 mm Gemini Column, NH4OH modifier) to obtain 4-(((3, 5-dicyano-4-ethyl-6-(4-methyl-1, 4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzamide (8 mg, 9%) as a white solid. LCMS m/z = 435 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta ppm 7.96 (br. s., 1H), 7.65-7.90 (m, J=8.36 Hz, 2H), 7.42- 7.65 (m, J=8.36 Hz, 2H), 7.37 (s, 1H), 4.55 (s, 2H), 3.81-3.90 (m, 4H), 2.78 (q, J=7.60 Hz, 2H), 2.55-2.62 (m, 2H), 2.43-2.48 (m, 2H), 2.21 (s, 3H), 1.84-1.98 (m, 2H), 1.22 (t, J=7.60 Hz, 3H).

Molecular Weight:214.06
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:212.97893
Monoisotopic Mass:212.97893
Topological Polar Surface Area:43.1
Heavy Atom Count:11
Complexity:141
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes