تفاعل #159372

معادلة التفاعل

3-oxetanamine hydrochloride

triphosgene

(S)-3-methyl-4-(1-methyl-5-(4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)morpholine

triethylamine

→

title compound

المردود 75.6%

(5)-1-(4-(1-methyl-7-(3-methylmorpholino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)-3-(oxetan-3-yl)urea

المردود 75.6%

المذيبات

EtOAc

1,2-dichoroethane

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 70° C. for 1 h
2. 2
   درجة الحرارةThe reaction mixture was cooled to RT
3. 3
   workup.STIRRINGThe reaction mixture was stirred at RT under N2 for 16 h
4. 4
   غسيلThe organic layer was washed with water and brine
5. 5
   تجفيفdried (Na2SO4)
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe crude was purified by column chromotagraphy (Si-PPC, gradient 50 to 100% EtOAc in heptane, followed by 0 to 30% methanol in dichloromethane)

الإجراء التجريبي

To a stirred solution of (S)-3-methyl-4-(1-methyl-5-(4-nitrophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)morpholine (50.0 mg, 0.154 mmol) in anhydrous 1,2-dichoroethane (5.0 mL) was added triethylamine (0.071 mL, 0.51 mmol, 3.3 eq.). The reaction was cooled to 0° C. and triphosgene (45.7 mg, 0.154 mmol, 1.0 eq) was added in one portion. After stirring at 0° C. under N2 for 5 minutes, the reaction mixture was stirred at 70° C. for 1 h. The reaction mixture was cooled to RT, and 3-oxetanamine hydrochloride (84.4 mg, 0.77 mmol, 5.0 eq.) was then added. The reaction mixture was stirred at RT under N2 for 16 h and then diluted with EtOAc (25 mL). The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified by column chromotagraphy (Si-PPC, gradient 50 to 100% EtOAc in heptane, followed by 0 to 30% methanol in dichloromethane). Trituration from methanol afforded the title compound (49.3 mg, 75.5%) as a solid. 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.76 (s, 1H), 8.25 (d, J=8.8 Hz, 2H), 8.21 (s, 1H), 7.50 (d, J=8.8 Hz, 2H), 6.97 (d, J=6.7 Hz, 1H), 4.85 to 4.69 (m, 3H), 4.44 (t, J=6.0 Hz, 2H), 4.23 to 4.12 (m, 4H), 3.96 to 3.81 (m, 2H), 3.72 (dd, J=14.7 Hz, 5.8 Hz, 1H), 3.69 to 3.58 (m, 2H), 3.50 (d, J=13.3 Hz, 1H), 1.26 (d, J=6.5 Hz, 3H); LC-MS m/z (method C1)=424.2 [M+H]+, RT=3.12 min.

المصدر