Ethyl 7-bromoisoquinoline-3-carboxylate

To a solution of 4-bromophthalic acid (3.0 g, 12.24 [MMOL)] in 30 mL of THF was added a solution of borane-THF complex (1. OM) dropwise at 0 [°C.] The solution was warmed to rt and stirred for 3 h. The reaction mixture was quenched by addition of HCI (2N) at 0 [°C.] The product was extracted with ethyl acetate and washed with sat. [NACI, ] dried over [NA2SC4, ] and concentrated under reduced pressure to afford 2.8 g (100percent) of 4-bromo-2- hydroxymethylbenzyl alcohol as a [COLORLESS OIL.APOS;H] NMR [(CDCK)] 7.28 (m, 2 H), 7.26 (m, 1 H), 4.69 (s, 4 H), 2.80 (bs, [2 H).] To a solution of oxalyl chloride (2.37 mL, 4.607 mmol) in DCM (20 mL) was added dropwise DMSO (1.95 mL) [AT-78 °C.] The mixture was stirred at-78 °C for 30 min and a solution of the diol (1.00 g, 4.607 [MMOL)] was added dropwise. The reaction mixture was stirred for 2 hr and TEA (11.5 mL) was added. The reaction mixture was warmed to rt and water was added. The organic layer was separated and washed with sat. NaCl, dried over Na2SO4, and concentrated under reduced pressure to give [4-BROMO-BENZENE-1, ] 2- dicarbaldehyde as a yellow oil (0.450 g, 46percent). A mixture of [4-BROMO-BENZENE-1, ] [2-DICARBALDEHYDE] (0.450 g, 2.137 mmol), diethylamino malonate (0.452 g, 2.137 mmol), and sodium ethoxide (0.218 g, 3.20 [MMOL)] in anhydrous ethanol (15 mL) was refluxed for 4 hr. The solution was cooled to rt and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (silica gel, 0. 5percent MeOH in [CHCI3)] to obtain 0.460 g (78percent) of the [7-BROMO-] isoquinoline-3-carboxylic acid ethyl ester which was [HYDROLYZED] according to general procedure C yielding the 0.350 g (85percent) of 7-bromo-isoquinoline-3-carboxylic acid as a white solid. LC/MS [(M/Z)] : 253 (M+1) [+.] [(2S)-AMINO-3-BIPHENYL-4YL-PROPIONIC] acid methyl ester (340 mg, 13.9 [MMOL)] was reacted with 7-bromo-isoquinoline-3-carboxylic acid (350 mg, 13.9 [MMOL)] as described in general procedure A. The resulting compound was hydrolyzed by following general procedure C yielding the title compound (132 mg, 81 percent) as a white solidTo a stirred solution of 4-bromophthalaldehyde (1 .6 g, 7.74 mmol, 1 .0 equiv) in ethanol (20 mL) was added diethyl 2-aminomalonate hydrochloride (1 .63 g, 7.74 mmol, 1 .0 equiv) and sodium ethoxide (3.9 mL, 1 1 .61 mmol, 1 .5 equiv) at room temperature, and the mixture was stirred for 4 h under nitrogen atmosphere at 80°C. The reaction mixture was cooled to room temperature and quenched with saturated ammonium chloride. The reaction mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic layers was dried over sodium sulphate and evaporated to obtain crude product. (0714) Run 2; To a stirred solution of 4-bromophthalaldehyde (1 .6 g, 7.74 mmol, 1 .0 equiv) in ethanol (20 mL) was added diethyl 2-aminomalonate hydrochloride (1 .63 g, 7.74 mmol, 1 .0 equiv) and sodium ethoxide (3.9 mL, 1 1 .61 mmol, 1 .5 equiv) at room temperature, and the mixture was stirred for 4 h under nitrogen atmosphere at 80°C. The reaction mixture was cooled to room temperature, and quenched with saturated ammonium chloride. The reaction mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic layers was dried over sodium sulphate and evaporated to obtain crude product. The crude products from Run 1 and Run 2 were combined and purified by silica gel flash column chromatography. The compound eluted out in 15 -25 percent EtOAc: Hexanes. The fractions were evaporated to obtain ethyl 7-bromoisoquinoline-3-carboxylate (1 .2 g, 28percent) as brown solid. To a solution of To a solution of

Molecular Weight:280.12
XLogP3:3.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:278.98949
Monoisotopic Mass:278.98949
Topological Polar Surface Area:39.2
Heavy Atom Count:16
Complexity:259
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes