تفاعل #338357

معادلة التفاعل

N-methylhydroxylamine hydrochloride

COMPOUND 249

Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Et3N

phosgene

DIPEA

→

COMPOUND 325

المردود 55.0%

4-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidine-1-carboxylic acid hydroxy-methyl-amide

المردود 55.0%

المذيبات

CH2Cl2

toluene

toluene

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةwas then warmed up to room temperature
2. 2
   أخرىsolvent was removed under reduced pressure (high vac.)
3. 3
   أخرىto yield a yellow solid
4. 4
   workup.STIRRINGThe mixture was stirred at room temperature for 17 hours
5. 5
   أخرىSolvent was removed under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (20 mL)
7. 7
   استخلاصextracted with saturated NaHCO3 (20 mL)
8. 8
   تجفيفdried over MgSO4
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated
11. 11
    أخرىThe crude material was purified by column chromatography on silica gel (9:1:0.1 CH2Cl2:MeOH:NH4OH)

الإجراء التجريبي

To a 0° C. solution of COMPOUND 249 (236 mg, 0.760 mmol) in toluene (20 mL) and Et3N (0.45 mL, 3.42 mmol) was added phosgene solution in toluene (20 wt %, 0.519 mL, 1.14 mmol). The mixture was stirred at 0° C. for 2 hours, was then warmed up to room temperature and solvent was removed under reduced pressure (high vac.) to yield a yellow solid. Half of the solid (0.380 mmol) was dissolved in CH2Cl2 (10 mL) and DIPEA (0.5 mL) was added followed by N-methylhydroxylamine hydrochloride (48 mg, 0.57 mmol). The mixture was stirred at room temperature for 17 hours. Solvent was removed under reduced pressure and the residue was dissolved in CH2Cl2 (20 mL), extracted with saturated NaHCO3 (20 mL), dried over MgSO4, filtered and concentrated. The crude material was purified by column chromatography on silica gel (9:1:0.1 CH2Cl2:MeOH:NH4OH) to provide COMPOUND 325 as white solid (81 mg, 55%). 1H NMR (CDCl3) δ 1.60-1.73 (m, 3H), 1.92-2.00 (m, 2H), 2.09 (s, 6H), 2.65-2.76 (m, 3H), 2.95 (s, 3H), 3.83 (s, 4H), 4.12-4.18 (m, 2H), 7.09 (dd, 2H, J=4.2, 7.5 Hz), 7.37 (d, 2H, J=7.5 Hz), 8.34 (d, 2H, J=4.2 Hz); 13C NMR (CDCl3) δ 18.0, 27.1, 44.3, 45.5, 54.6, 57.4, 122.5, 133.4, 138.2, 145.9, 157.0, 165.8; ES-MS m/z 384 (M+H). Anal. Calcd. for C21H29N5O2.0.2H2O.0.5 CH2Cl2: C, 60.12; H, 7.13; N, 16.30. Found: C, 60.06; H, 7.09; N, 16.32.

المصدر