반응 #633204

반응 방정식

2,6-lutidine

oxalylchloride

2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

1-benzyl-1H-pyrazol-3-ylamine

→

N-(1-benzyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

수율 69.3%

용매

methylene chloride

methylene chloride

반응 조건

후처리

1. 1
   workup.WAITAfter 1 h
2. 2
   workup.WAITto proceed for 16 h
3. 3
   세척The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution
4. 4
   건조dried over sodium sulfate
5. 5
   농축concentrated in vacuo
6. 6
   기타purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)

실험 절차

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, crude 1-benzyl-1H-pyrazol-3-ylamine (0.42 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford N-(1-benzyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (101 mg, 69%) as a white solid: ESI-LRMS m/e calcd for C25H28ClN3O3S [M+] 485.2, found 486.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.18 (m, 2H, CH2), 1.40-1.91 (m, 8H, 4×CH2), 2.10-2.31 (m, 1H, CH), 3.23 (s, 3H, SO2CH3), 3.56 (t, J=7.6 Hz, 1H, CH), 5.12 (s, 2H, NCH2), 6.69 (d, J=2.3 Hz, 1H, Ar), 7.12 (dd, Jo=7.2, Jm=1.7 Hz. 2H, Ar), 7.26-7.33 (m, 4H, Ar), 7.43 (dd, Jo=8.2, Jm=1.6 Hz. 1H, Ar), 7.57 (d, Jm=1.6 Hz, 1H, Ar), 8.04 (d, Jo=8.2 Hz. 1H, Ar), 8.27 (brs, 1H, NH).

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