تفاعل #2161266

معادلة التفاعل

[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

المذيبات

DMA

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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)+.

المصدر