تفاعل #47437

معادلة التفاعل

(S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine

benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate

→

(S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

المردود 53.5%

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvents were evaporated
2. 2
   workup.ADDITIONThe residue was treated with ethyl acetate and ammonium chloride solution
3. 3
   أخرىthe organic layer separated
4. 4
   غسيلThe organic layer was washed with brine
5. 5
   تجفيفdried over sodium sulfate
6. 6
   أخرىThe solvents were evaporated
7. 7
   أخرىthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 0% to 80% ethyl acetate/hexanes) which

الإجراء التجريبي

To a solution of (S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.140 g, 0.37 mmol) in N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.090 g, 0.46 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.655 g, 1.48 mmol). The mixture was stirred at room temperature overnight and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 0% to 80% ethyl acetate/hexanes) which afforded (S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.110 g, 53%) as a white solid: HR-ES-MS m/z calculated for C29H38FN5O5 [M+H]+ 556.2930, observed 556.2928, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H), 1.25 (s, 3H), 1.29, 1.31 (2×s, 3H), 1.35-1.64 (m, 2H), 1.66-1.83 (m, 1H), 1.84-1.95 (m, 4H), 3.29-3.39 (m, 4H), 3.73 (dd, J=8.3, 5.9 Hz, 1H), 4.00 (dd, J=8.3, 6.5 Hz, 1H), 4.04-4.14 (m, 2H), 4.18 (d, J=18.4 Hz, 1H), 4.25-4.41 (m, 1H), 4.56 (d, J=18.4 Hz, 1H), 4.84-4.93 (m, 2H), 6.43 (d, J=2.1 Hz, 1H), 6.59-6.70 (m, 2H), 7.03 (t, J=8.2 Hz, 1H), 7.60 (br. s., 1H), 10.79 (s, 1H).

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