Реакция #2161265

Уравнение реакции

[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid

HOBt

EDCI

NMM

1-piperidin-4-ylpyrrolidin-2-one hydrochloride

→

title compound

1(1-{[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)pyrrolidin-2-one

Растворители

DMA

Условия реакции

Обработка

1. 1
   Другоеthe mixture sonicated to a fine suspension
2. 2
   ДругоеThe volatiles were removed under high vacuum
3. 3
   Другоеthe residue partitioned between EtOAc (70 mL) and water (25 mL)
4. 4
   ДругоеThe aqueous layer was removed
5. 5
   Промывкаthe organics washed with NaHCO3 (30 mL), brine (30 mL)
6. 6
   Сушкаdried over MgSO4
7. 7
   Фильтрацияfiltered

Методика

To a solution of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (164 mg, 0.53 mmol) in DMA (3 mL) at room temperature was added HOBt (78 mg, 0.58 mmol), EDCI (111 mg, 0.58 mmol), NMM (0.20 mL, 1.84 mmol) and 1-piperidin-4-ylpyrrolidin-2-one hydrochloride (150 mg, 0.73 mmol) and the mixture sonicated to a fine suspension and stirred for 64 hours at room temperature. The volatiles were removed under high vacuum and the residue partitioned between EtOAc (70 mL) and water (25 mL). The aqueous layer was removed and the organics washed with NaHCO3 (30 mL), brine (30 mL), dried over MgSO4, filtered and stripped to yield the title compound as an off-white solid, 123 mg, 51%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.51-8.54 (2 H, m), 7.64-7.69 (2 H, m), 7.25-7.35 (2 H, m), 7.11-7.21 (2 H, m), 6.53 (1 H, s), 5.11-5.28 (2 H, m), 4.37 (1 H, d, J=13.14 Hz), 3.90-4.05 (4 H, m), 3.23-3.31 (2 H, m), 3.08-3.20 (1 H, m), 2.57-2.70 (1 H, m), 2.22 (2 H, t, J=8.08 Hz), 1.84-1.95 (2 H, m), 1.40-1.73 (4 H, m); m/z (APCI+) for C26H28N5O2F 462.2 (M+H)+.

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