N-[5-[(4-Boc-1-piperazinyl)methyl]-2-pyridyl]-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-6-benzimidazolyl)pyrimidin-2-amine synthesis

6synthesis methods

Product Name:N-[5-[(4-Boc-1-piperazinyl)methyl]-2-pyridyl]-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-6-benzimidazolyl)pyrimidin-2-amine
CAS Number:1231930-48-5
Molecular formula:C30H36F2N8O2
Molecular Weight:578.66

1231930-42-9 Synthesis

1H-BenziMidazole, 6-(2-chloro-5-fluoro-4-pyriMidinyl)-4-fluoro-2-Methyl-1-(1-Methylethyl)-

1231930-42-9
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tert-butyl 4-((6-aminopyridin-3-yl)methyl)piperazine-1-carboxylate

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N-[5-[(4-Boc-1-piperazinyl)methyl]-2-pyridyl]-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-6-benzimidazolyl)pyrimidin-2-amine

1231930-48-5
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Yield:1231930-48-5 87%

Reaction Conditions:

with tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;Cs₂CO₃;4,5-bis(diphenylphosphino)-9,9-dimethylxanthene in tert-butyl alcohol at 110; for 8 h;Inert atmosphere;

Steps:

5.2 tert-butyl 4-((6-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazine-1-carboxylate (2-20)

To a suspension of 6-(2-chloro-5-fluoropyrimidin-4-yl)-4-fluoro-l-isopropyl-2- methyl-lH-benzo[d]imidazole (2-18, 258 mg, 0.8 mmol), tert-butyl 4~((6~aminopyridin-3- yl)methyl)piperazine-l-carboxylate (2-19, 350.6 mg, 1.2 mmol) and Cs₂COs (782 mg, 2.4 mmol) in 5 mL of -BuOH were added Pd2(dba)3 (73.3 mg, 0.08 mmol) and Xantphos (23 mg, 0.04 mmol) under an atmosphere of N₂. The mixture was heated to i l0°C and stirred for 8h. The mixture was then cooled to room temperature, extracted with CHCta and isopropanoi (V7V=4: 1), and the combined organic layers were washed with brine, dried over anhydrous Na₂S0₄, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% MeOH in DCM) to give fe/ -butyl 4-((6-(5- fluoro-4-(4-fluoro-l-isopropyl-2-memyl-lH-benzo|^"d]inudazol-6-yl)pyrimidin-2- ylamino)pyridin-3-yl)methyl)piperazine-l-carboxyiate 2-20 as a white solid (403 mg, 87%). LCMS: m/z 579,3 [M+ 1 ] .

References:

WO2017/185031,2017,A1 Location in patent:Page/Page column 96; 97