Diisopropylethylamine → 3-Bromo-5-{[butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}benzamide Dihydrochloride

Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoate prepared by the method in EXAMPLE SP-190, Step 1 (170 mg, 0.54) is dissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL), and lithium hydroxide monohydrate is added (45 mg, 1.1 mmol), and the reaction stirred 16 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (375 μL, 2.16 mmol), HATU (256 mg, 0.68 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in EXAMPLE SP-272 (265 mg, 0.65 mmol) are added. The reaction stirred at room temperature 1 h. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (1 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 616.2 [M+H]+.

1. additionis added (45 mg, 1.1 mmol)
2. concentrationThe solution is concentrated under reduced pressure
3. dissolutionThe residue is redissolved in DMF (5 mL)
4. additionare added
5. stirringThe reaction stirred at room temperature 1 h
6. washwashed with water, and saturated sodium bicarbonate
7. dry with materialdried (sodium sulfate)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

ORD 기록

ord-11ac6f0e227c42f882ed4027d76c3999

출처 데이터셋

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07176242B2