2-(3-Bromophenyl)-1,3-dioxolane

Ethyl (S)-3-83APOS;-[(BENZOYLMETHYLAMINO)- methyl] BIPHENYL-4-YL}-2-(2-BENZOYLPHENYLAMINO)- propionate a. 2- (3-BROMOPHENYL) [1, 3] dioxolane 870 g (4.56 mol) of 3-bromobenzaldehyde, 2.6 1 (45.6 mol) of 1, 2-ethanediol, and 87 g (0.46 mol) of p-toluenesulphonic acid are dissolved in 4 1 of toluene. After refluxing for 5 h 30, 1 1 of an aqueous 1N sodium hydroxide solution is added at ambient temperature. The mixture obtained is filtered through celite, and the organic phase is recovered and washed with 2 1 of water. The solvents are evaporated off and 1 060 g of acetal are obtained with a quantitative yield. b. 3-Boronic acid-benzaldehyde In a manner similar to the preparation of tert-butyl (3-boronic acid-phenyl) methylcarbamate (Example LD), using 819 g (3.57 mol) of 2- (3-BROMO- phenyl) [1, 3] dioxolane, 355 g of crude product is used without purification in the following step. c. Ethyl (S)-2-TERT-BUTOXYCARBONYLAMINO-3- (3APOS;-FORMYL- biphenyl-4-yl) propionate In a manner similar to the preparation of ethyl (S)-2-TERT-BUTOXYCARBONYLAMINO-3- [3APOS;- (TERT- butoxycarbonylmethylamino) BIPHENYL-4-YL] PROPIONATE (Example LE), using 173 g (391 mmol) of ethyl (S)- 2-TERT-BUTOXYCARBONYLAMINO-3- (4-TRIFLUOROMETHANE- sulphonyloxyphenyl) propionate and 82 g (547 mmol) of 3-boronic acid-benzaldehyde, 95.7 g of coupled product are isolated with a 61percent yield. d. Ethyl (S)-2-TERT-BUTOXYCARBONYLAMINO-3- (3APOS;-METHYL- aminomethylbiphenyl-4-yl) propionate 21.2 g (314 mmol) of methylamine hydrochloride are introduced into a solution containing 25 g (63.0 mmol) of ethyl (S)-2-tert- BUTOXYCARBONYLAMINO-3- (3APOS;-FORMYLBIPHENYL-4-YL)- propionate in 200 ml of methanol. After stirring for 30 min at ambient temperature, 6.0 g (95.4 mmol) of sodium cyanoborohydride are added portionwise. The reaction medium is stirred for 16 h and the solvents are evaporated off. The residue is dissolved in ethyl acetate, and the organic phase is washed with water and then dried over magnesium sulphate and concentrated. The crude product is purified by chromatography on a column of. silica and eluted with a heptane/ethyl acetate and then a methanol/ethyl acetate mixture. 10 g of the expected amine are isolated with a 38percent yield. e. Ethyl (S)-3- {3APOS;- [ (BENZOYLMETHYLAMINO) METHYL]- BIPHENYL-4-YL}-2-TERT-BUTOXYCARBONYLAMINOPROPIONATE 4.2 ml (36.3 mmol) of benzoyl chloride are added to a solution containing 10 g (24.3 mmol) of ethyl (S)-2-TERT-BUTOXYCARBONYLAMINO-3- (3APOS;-METHYL- aminomethylbiphenyl-4-yl) propionate and 10.1 ml (72.6 mmol) of triethylamine in 100 ml of tetrahydrofuran. The medium is stirred for 3 h and then hydrolysed, extracted with ethyl acetate, dried over magnesium sulphate, and concentrated. The residue obtained is purified by chromatography on a column of silica and eluted with a 3/2 heptane/ethyl acetate mixture. 8.0 g of expected amide are obtained with a 64percent yield. f. Ethyl (S)-2-AMINO-3-F3APOS;- [ (BENZOYLMETHYLAMINO)- METHYL] BIPHENYL-4-YL} PROPIONATE 8.0 G (15.5 mmol) of ethyl (S)-3- {3APOS;- [ (BENZO. YLMETHYLAMINO) methyl] BIPHENYL-4-YL}-2-TERT- butoxycarbonylaminopropionate are dissolved in 70 ml of dichloromethane. 12 ml (157 mmol) of trifluoroacetic acid are added in small amounts. The medium is stirred for 16 h and then brought to pH 9 with sodium carbonate, extracted with dichloromethane, dried over magnesium sulphate, and concentrated. The residue obtained is purified by chromatography on a column of silica and. eluted with a 1/1 heptane/ethyl acetate mixture. 5.2 g of expected amine are obtained with an 82percent yield. G. ETHYL (S)-3-{3APOS;-[(BENZOYLMETHYLAMINO) METHYL]- biphenyl-4-yl}-2-(2-benzoylphenylamino) propionate In a manner similar to the preparation of the ETHYL (S)-2- (2-BENZOYLPHENYLAMINO)-3- (3APOS;-METHYLAMINO- biphenyl-4-yl) propionate (Example LG), using 3.8 g (9.13 mmol) of ethyl (S)-2-AMINO-3-{3APOS;-[(BENZOYLMETHYL- amino) methyl] BIPHENYL-4-YL} PROPIONATE, 1.3 g of ethyl Preparation Example 90. 2-(m-Bromophenyl)-1, 3-dioxolane EXAMPLE IX

Molecular Weight:229.07
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:18.5
Heavy Atom Count:12
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes