تفاعل #161926

معادلة التفاعل

#50

N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Brop

diisopropylethylamine

1-aminocyclohexanecarboxylic acid

→

#52

المردود 35.5%

1-amino-N-[(2S)-1-{[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrroli din-1-yl}-5-methyl-1-oxoheptan-4-yl] (methyl)amino}-3-methyl-1-oxobutan-2-yl]cyclohexanecarboxamide

المردود 35.5%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe mixture was quenched with water
2. 2
   استخلاصextracted twice with ethyl acetate
3. 3
   تجفيفThe combined organic layers were dried over sodium sulfate
4. 4
   ترشيحfiltered
5. 5
   تركيزconcentrated in vacuo
6. 6
   أخرىThe residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane)

الإجراء التجريبي

To a solution of #50 (120 mg, 0.18 mmol, 1 eq.), Brop (84 mg, 0.21 mmol, 1.2 eq.) and diisopropylethylamine (0.1 mL, 0.54 mmol, 3 eq.) in dichloromethane (15 mL, 0.009 M) at 0° C. was added 1-aminocyclohexanecarboxylic acid (31 mg, 0.21 mmol, 1.2 eq.). After 2 hours, the mixture was quenched with water and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane) to give #52 (50 mg, 35%). Rf 0.6 (10% methanol in dichloromethane). LC-MS (Protocol K): m/z 783.79 [M+H+]; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.64 (br d, J=8 Hz) and 8.87 (br d, J=9 Hz), total 1H], 8.18-8.28 (m, 1H), [7.77 (d, J=3.5 Hz) and 7.80 (d, J=3.3 Hz), total 1H], [7.63 (d, J=3.3 Hz) and 7.66 (d, J=3.3 Hz), total 1H], 7.12-7.31 (m, 5H), 5.35-5.43 and 5.49-5.57 (2 m, total 1H), [4.51 (dd, J=9, 8 Hz), and 4.61 (dd, J=9, 7 Hz), total 1H], 3.16, 3.19, 3.21 and 3.25 (4 s, total 6H), 2.93 and 3.02 (2 br s, total 3H), [1.05 (d, J=6.8 Hz) and 1.10 (d, J=6.8 Hz), total 3H].

المصدر