2-Boc-amino-4-formylpyridine

To a solution of the product of Step 2 (19.15 g, 85.5 [MMOL)] in [CH2CI2] (640 ml) was added a saturated aqueous solution of [NAHC03] (8.62 g, 103 [MMOL)] and NaBr (444 mg, 4.3 [MMOL).] The reaction mixture was cooled to 0 [°C, ] and TEMPO (140 mg, 0.90 [MMOL)] was introduced. Upon vigorous stirring, commercial bleach solution (122 [ML, ] 0.7 [M, ] 85.4 [MMOL)] (5.25percent in NaOCI) was added portionwise over 40 min. After an additional 20 min at 0 [°C, ] the reaction mixture was quenched with saturated aqueous Na2S203 and allowed to warm to 23 [°C.] Dilution with water and extraction with CH2CI2, followed by concentration and flash chromatography (eluant : 30percent [HEXANES-CH2CI2] to 0-2percent [ACETONE-CH2CI2)] afforded 15.97 g (71.9 [MMOL] ; 84percent yield) of the aldehyde as an off-white solid.To a solution of compound A2 (19.15 g, 85.5 mmol) in CHTo a solution of 19.15 g (85.5 mmol) of alcohol 2 A in 640 ml of CHTo a solution of compound 64.8 (7 g, 31.21 mmol, 1 eq) in DCM (60 mL) wasadded Dess-Martin periodinane (19.9 g, 46.8 mmol, 14.5 mL, 1.5 eq) portion-wise at 18 °Cunder N2. The mixture was stirred at 18 °C for 2 hours. The reaction mixture was diluted with H20 (60 mL) and extracted with DCM (50 mL x 3). The combined organic layers were washed with brine (100 mL x 1), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate=5:1) to give compound 64.7 (5.8 g, 26.1 mmol, 84percent yield) as a white solid. ‘H NMR (400 MI-Iz, DMSO-d6) ö: 1.49 (s, 9 H), 7.42 (dd, J=4.96, 0.99 Hz, 1 H), 8.25 (s, 1 H), 8.50 (d, J=4.85 Hz, 1 H), 10.04 (s, 1 H) and 10.12 (s, 1 H) ppm.Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn02 were added. The mixture was leftunder agitation overnight at 70 °C then the solids were removed by filtering. The filtrate was evaporated to dryness to yield 1.4 g (57 percent) of compound 2G in the form of a white solid.Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn02 were added. The mixture was leftunder agitation overnight at 70 °C then the solids were removed by filtering. The filtrate was evaporated to dryness to yield 1.4 g (57 percent) of compound 2G in the form of a white solid.Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn02 were added. The mixture was leftunder agitation overnight at 70 °C then the solids were removed by filtering. The filtrate was evaporated to dryness to yield 1.4 g (57 percent) of compound 2G in the form of a white solid.Compound 2G: tert—butyl (4—formylpyridin—2—yl)carbamate Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn02 were added. The mixture was leftunder agitation overnight at 70 °C then the solids were removed by filtering. The filtrate was evaporated to dryness to yield 1.4 g (57 percent) of compound 2G in the form of a white solid.Compound 2G: tert-butyl (4-formylpyridin-2-yl)carbamate Compound 2F (2.5 g, 1 1.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn0Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then 19.4 g (223.14 mmol, 20.02 equiv) of Mn0Compound 2G: tert-butyl (4-formylpyridin-2-yl)carbamate Compound 2F (2.5 g, 11.15 mmol, 1.00 equiv) was dissolved in DCE (25 mL) then19.4 g (223.14 mmol, 20.02 equiv) of Mn02 were added. The mixture was left under agitationovernight at 70 °C then the solids were removed by filtering. The filtrate was evaporated to dryness to yield 1.4 g (57 percent) of compound 2G in the form of a white solid.To a solution of compound 54.7 (1.49 g, 4.50 mmol, 1 eq) in DCM (15 mL) wasadded DBU (1.03 g, 6.75 mmol, 1.02 mL, 1.50 eq) in one portion at 18C underN2. Themixture was stirred at 18 C for 0.5 hour, then to the mixture was added compound 54.8(1 g, 4.50 mmol, 1 eq) in one portion at 18 C, then was stirred at 18 C for 0.5 hour. The reactionmixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate=1:1) to give compound 54.6 (1.90 g, 4.44 mmol, 98.78% yield) as a white solid.To a mixture of compound 21.8 (2.50 g, 11.25 mmol, 1 eq) and methyl 2- dimethoxyphosphorylacetate 21.7 (2.05 g, 11.25 mmol, 1.63 mL, 1 eq) in THF (30 mL) was added K2C03 (3.11 g, 22.50 mmol, 2 eq) in one portion at 50C under N2. The mixture was stirred at 50 C for 15 hours. The reaction mixture was diluted with H20 30 mL and extracted with EtOAc 90 mL (30 mL x 3). The combined organic layers were washed with brine 50 mL(50 mL x 1), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate=5:1) to give compound 21.6 (2.40 g, 8.62 mmol, 76.62% yield) as a white solid.[02921 LCMS (ESI): m/z: [M + H] calcd for C14H18N204: 278; found 279; RTO.739 mm.

Molecular Weight:222.24
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:222.10044231
Monoisotopic Mass:222.10044231
Topological Polar Surface Area:68.3
Heavy Atom Count:16
Complexity:260
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes