4-BROMO-2-METHOXY-6-METHYLPYRIDINE

Diisopropyl diazocarboxylate (323 mg, 1.60 mmol) was added to a solution of 4- bromo-6-methylpyridin-2-ol (200 mg, 1.06 mmol), methanol (54 ^L, 1.3 mmol) and triphenylphosphine (419 mg, 1.60 mmol) in THF (4.6 mL). The reaction mixture was stirred at r.t. for 18 h. Ethyl acetate was added and the mixture was washed with 1N NaOH (3x). The organic layer was dried with sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel using a solution of ethyl acetate in hexanes (5 to 10percent) to give the title compound (65 mg, 0.32 mmol, 30percent).Diisopropyl diazocarboxylate (323 mg, 1.60 mmol) was added to a solution of 4- bromo-6-methylpyridin-2-ol (200 mg, 1.06 mmol), methanol (54 iL, 1.3 mmol) and triphenylphosphine (419 mg, 1.60 mmol) in THF (4.6 mL). The reaction mixture was stirred at r.t. for 18 h. Ethyl acetate was added and the mixture was washed with 1 N NaOH (3x). The organic layer was dried with sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel using a solution of ethyl acetate in hexanes (5 to 10percent) to give the title compound (65 mg, 0.32 mmol, 30percent).A 0.36 M solution of intermediate 6a in THF (42 mL, 15.12 mmol) was added to a stirred mixture of NaO/-Bu (31.0 mg, 0.32 mmol) was added to a stirred suspension of Pd2dba3 (5.91 mg, 6.46 pmol) and /-BuXPhos (8.22 mg, 19.4 umol) in l, 4-dioxane (15 mL) in a sealed tube and under N2 atmosphere at room temperature. The reaction mixture was stirred at 95 C for 5 min, then a mixture of intermediate 1-90 (45.0 mg, 0.16 mmol) and 4- bromo-2-methoxy-6-methylpyridine (CAS: 1083169-00-9; 26.1 mg, 0.13 mmol) in l, 4dioxane (5 mL) was added to the reaction mixture under N2 atmosphere at 95 C. The reaction mixture was stirred at 100 C for 1.5 h. The mixture was diluted with NaHC03 (sat., aq.) and extracted with DCM. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude mixture was purified by reverse phase ([65mM NEEOAc/ACN (90:lO)]/[ACN:MeOH (1 :1)], gradient from 90:10 to 54:46). The residue (18 mg) was taken into DCM and treated with HC1 (4N in l, 4-dioxane, 1 eq). The solvents were evaporated in vacuo to afford compound 109 (16 mg, 26%) as a white solid.NaO/-Bu (119 mg, 1.24 mmol) was added to a stirred suspension of Pd2dba3 (22.7 mg, 24.7 nmol) and /BuXPhos (31.5 mg, 74.2 pmol) in l, 4-dioxane (15 mL) in a sealed tube and under N2 atmosphere at room temperature. The reaction mixture was stirred at 95 C for 5 min, then a mixture of (S)-(+)-3-amino- 1 -boc-pipcrdinc [625471-18-3] (129 mg, 0.64 mmol) and Intermediate 1 (42 mL, 15.12 mmol), followed by A, A, N', N'- Tetramethylethylenediamine (CAS 110-18-9, 2.44 mL, 16.3 mmol) and (0304) bis(triphenylphosphine)palladium(II)dichloride (CAS 13965-03-2, 0.22 g, 0.31 mmol) were added to General procedure: l-Boc-3-hydroxypiperidine (CAS 85175-45-2, 0.41 g, 2.05 mmol) was stirred in DMF (1.65 mL), at rt, and then a 60% NaH dispersion in mineral oil (0.082 g, 2.05 mmol) was added. Then 4-chloro-2, 6-dimethylpyridine (CAS 3512-75-2, 0.26 mL, 2.05 mmol) in DMF (0.64 mL) was added dropwise at rt. The mixture was stirred overnight at 60 C. The mixture was evaporated diluted with FLO and was extracted with EtOAc. The organic layer was separated, dried (Na2S04), filtered and evaporated, in vacuo. The residue was purified by flash column chromatography (silica; EtOAc in heptane 0/100 to 30/70). The desired fractions were collected and concentrated in vacuo to yield intermediate 22 (0.32 g, 51%) as a colorless oil(0363) Intermediate 24 was prepared following an analogous procedure to the one described for the synthesis of intermediate 22 using

Molecular Weight:202.05
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:200.97893
Monoisotopic Mass:200.97893
Topological Polar Surface Area:22.1
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes