تفاعل #1185443

معادلة التفاعل

citric acid

Sodium hydride

(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-fluoropyridin-2-yl)-2-hydroxypropanamide

4-chloro-1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine

→

product

المردود 82.1%

(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide

المردود 82.1%

المذيبات

THF

water

EtOAc

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to room temperature
2. 2
   workup.STIRRINGstirred overnight
3. 3
   أخرىThe organic layer was separated
4. 4
   استخلاصthe aqueous layer re-extracted with EtOAc (2×50 mL)
5. 5
   غسيلThe combined organics were washed with saturated brine (75 mL)
6. 6
   تجفيفdried (MgSO4)
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated in vacuo
9. 9
   أخرىThe crude product was purified by flash silica chromatography, elution gradient 25 to 100% EtOAc in isohexane

الإجراء التجريبي

Sodium hydride (60% dispersion in mineral oil) (83 mg, 2.07 mmol) was added to (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-fluoropyridin-2-yl)-2-hydroxypropanamide (Intermediate BA2) (500 mg, 1.04 mmol) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2,6-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate BA3) (310 mg, 1.04 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was adjusted to pH 7 by addition of 1M citric acid and the reaction mixture diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×50 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 25 to 100% EtOAc in isohexane to afford the product (637 mg, 82%). 1H NMR (400 MHz, CDCl3) δ 0.99 (9H, t), 3.69-3.72 (2H, m), 3.82 (2H, t), 4.16-4.24 (2H, m), 6.06 (1H, t), 7.31-7.47 (8H, m), 7.52-7.55 (2H, m), 7.63-7.66 (4H, m), 8.12 (1H, d), 8.26-8.29 (1H, m), 8.42 (1H, s), 8.58 (1H, s), 8.79 (1H, s).

المصدر