Реакция #2161266

Уравнение реакции

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

HOBt

EDCI

NMM

4-(methylsulfonyl)piperidine

→

title compound

4-(5-(4-fluorobenzyl)-1-{2-[4-(methylsulfonyl)piperidin-1-yl]-2-oxoethyl}-1H-pyrazol-3-yl)pyridine

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 (150 mg, 0.48 mmol) in DMA (3 mL) at room temperature was added HOBt (72 mg, 0.53 mmol), EDCI (102 mg, 0.53 mmol), NMM (0.13 mL, 1.20 mmol) and 4-(methylsulfonyl)piperidine (117 mg, 0.72 mmol) and the mixture sonicated to a fine suspension and stirred for 18 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, 144 mg, 66%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.46-8.56 (2 H, m), 7.60-7.71 (2 H, m), 7.25-7.37 (2 H, m), 7.07-7.19 (2 H, m), 6.53 (1 H, s), 5.10-5.41 (2 H, m), 4.40 (1 H, d, J=13.14 Hz), 3.97-4.15 (1 H, m), 3.95 (2 H, s), 3.34-3.49 (1 H, m), 3.12 (1 H, t, J=12.00 Hz), 2.96 (3 H, s), 2.64 (1 H, t, J=11.62 Hz), 2.06 (2 H, d, J=12.88 Hz), 1.59-1.79 (1 H, m), 1.36-1.54 (1 H, m); m/z (APCI+) for C23H25N4O3F 457.1 (M+H)+.

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