Diethylamine → N,2-dimethylalanyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert-butoxy-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

To a stirring solution of #129 (823 mg, 0.826 mmol, 1.00 eq.) in 15 mL of dichloromethane, diethylamine (4 mL, 40 mmol, 50 eq.) was added. The reaction was allowed to stir at room temperature for ˜14½ hours. The reaction was concentrated in vacuo and azeotroped once with heptanes. Residue with diluted with dichloromethane and a small amount of methanol before being reduced down onto silica. Residue was purified by Silica Chromatography (Gradient: 0%-20% methanol in ethyl acetate) producing #130 (518 mg, 81%) as a white solid. LC-MS (Protocol Q): m/z 774.3 [M+H+] retention time=1.48 minutes. HPLC (Protocol A at 25° C.): m/z 774.5 [M+H+], retention time=7.733 minutes (purity >98%). 1H NMR (400 MHz, DMSO-d6), δ 8.36 (d). 8.14 (d), 7.81 (t), 7.14-7.25 (m), 7.01-7.07 (m), 4.87-4.94 (m), 4.78-4.85 (m), 4.67-4.76 (m), 4.46-4.65 (m), 4.29-4.40 (m), 3.93-4.03 (m), 3.70-3.81 (m), 3.49-3.60 (m), 3.38-3.47 (m), 3.29-3.36 (m), 3.15-3.28 (m), 2.98-3.13 (m), 2.94 (br s), 2.74-2.89 (m), 2.64-2.69 (m), 2.18-2.45 (m), 2.02-2.14 (m), 1.90-2.01 (m), 1.62-1.87 (m), 1.40-1.55 (m), 1.37 (d), 1.20-1.33 (m), 1.16 (d), 1.01-1.10 (m), 0.90-0.98 (m), 0.82-0.89 (m), 0.69-0.79 (m).

1. concentrationThe reaction was concentrated in vacuo
2. customazeotroped once with heptanes
3. additionResidue with diluted with dichloromethane
4. customResidue was purified by Silica Chromatography (Gradient: 0%-20% methanol in ethyl acetate)

ORDレコード

ord-1e436e010a5d4c2aac06636d77650a63

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09138486B2