반응 #47342

반응 방정식

(S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

p-toluenesulfonic acid monohydrate

→

(S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide

수율 72.5%

용매

methanol

반응 조건

후처리

1. 1
   농축At this time, the reaction was concentrated in vacuo
2. 2
   workup.ADDITIONThe residue was diluted with dichloromethane (25 mL)
3. 3
   세척was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL), water (1×25 mL)
4. 4
   건조a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate
5. 5
   여과filtered
6. 6
   세척rinsed with dichloromethane
7. 7
   농축concentrated in vacuo
8. 8
   기타Purification by Analogix flash chromatography (8 g, 1-10% methanol/dichloromethane)

실험 절차

A solution of (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (43 mg, 0.08 mmol) in methanol (1 mL) at 25° C. was treated with p-toluenesulfonic acid monohydrate (4 mg, 0.02 mmol). The reaction was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was diluted with dichloromethane (25 mL) and was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL), water (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate, filtered, rinsed with dichloromethane and concentrated in vacuo. Purification by Analogix flash chromatography (8 g, 1-10% methanol/dichloromethane) afforded (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (28 mg, 71%) as a white solid: HR-ES-MS m/z calculated for C26H34N4O5 [M+H]+ 483.2602, observed 483.2603; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 1.46 (br. s., 1H), 1.53-1.65 (m, 1H), 1.65-1.85 (m, 5H), 2.57 (br. s., 2H), 2.76 (br. s., 2H), 3.21-3.31 (m, 2H), 3.72-3.82 (m, 1H), 3.87 (dd, J=13.4, 7.5 Hz, 1H), 4.09 (dd, J=13.6, 4.0 Hz, 1H), 4.18 (d, J=18.3 Hz, 1H), 4.56 (d, J=18.3 Hz, 1H), 4.65 (s, 1H), 4.71 (t, J=5.4 Hz, 1H), 4.87 (dd, J=10.7, 4.9 Hz, 1H), 4.93 (d, J=5.1 Hz, 1H), 6.41 (d, J=2.1 Hz, 1H), 7.04 (d, J=7.7 Hz, 2H), 7.18 (t, J=7.7 Hz, 1H), 7.53 (d, J=2.1 Hz, 1H), 10.75 (s, 1H).

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