5-CHLORO-2-FORMYLPYRIDINE

5-Chloro-pyridine-2-carboxylic acid ethyl ester (146 mg, 76. [3percent)] was obtained obtained as described in from 5-chloro-pyridine-2-carboxylic acid (200 mg, 1.03 mmol) with ethanol (3 mL) and 4M [HC1] in dioxane (0.5 mL) at 90 [°C] for 20 h. 5-Chloro-pyridine-2-carbaldehyde (58 mg, 52percent) was obtained as described in from 5-chloro-pyridine-2-carboxylic acid ethyl ester (146 mg, 0.786 mmol) with 1 M DIBAL in toluene (1.74 mL, 1.74 mmol) in dichloromethane (4.0 mL) 20 min. GC-MS [(M+)] : 141Isopropyl magnesium chloride (1 1. 5 ml_, 2 M in THF, 23 mmol) was added dropwise to a cold (-15°C) solution of 5-chloro-2-iodo-pyridine (5 g, 20.9 mmol) in THF (35 ml_). The mixture was stirred for 1 h at -15°C. DMF (2.3 g, 31.3 mmol) was added dropwise keeping the internal temperature below 0°C. The mixture was allowed to warm to rt, stirred for 1 h, cooled to 0°C, quenched by addition of a saturated aqueous solution of ammonium chloride, and extracted with EtOAc. The organic layer was washed with brine, dried (NaGeneral procedure: To the solution of 3a-k (0.64 mmol) in ethanol containing aceticacid (0.064 mmol), appropriate aldehyde or ketone (0.77 mmol)was added. The mixture was kept at room temperature for 2 h, theformed precipitation was filtered, and the left residue was washedwith ethanol to give compounds 4a-f and 5a-v as solid in 45-85%yield.To a solution of methyl (S)-6-(ethylamino)-2-((R)-2-(4-fluorophenyl)-2-methoxyethyl)hexanoate (87 mg, 0.26 mmol) in 5 ml_ DCE was added 5-chloropicolinaldehyde (51 mg, 0.35 mmol) followed by NaBH(OAc)3 (73 mg, 0.35 mmol) and AcOH (18.7 mg, 1 .2 mmol) at room temperature. The mixture was stirred for 8 h at the room temperature. The reaction was quenched by pouring into 10 ml_ 5% aqueous NaOH and diluted with ethyl acetate. The mixture was extracted with more ethyl acetate (3 x 20 ml_) and the combined organic layers washed with brine (2 x 20 ml_) and dried over Na2S04. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography (silica gel) eluting with 0% to 30% ethyl acetate/ hexane and 0% to 15% MeOH/DCM to give 89 mg of the title compound as a light yellow oil. LC/MS (Method A): tR = 4.4 min. MS (API-ES) m/z 465 (M+FT)

Molecular Weight:141.55
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:140.9981414
Monoisotopic Mass:140.9981414
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes