Diisopropylethylamine → 3-{[Butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-5-methylbenzamide Dihydrochloride

HRID 348908

반응식

HRID 348908 반응식
[CH2:1]([N:5]([CH2:7][C:8]1[CH:9]=[C:10]([CH:15]=[C:16]([CH3:18])[CH:17]=1)[C:11]([O:13]C)=O)[CH3:6])[CH2:2][CH2:3][CH3:4].O.[OH-].[Li+].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[ClH:55].Cl.[NH2:57][C@@H:58]([CH2:72][C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[C:75]([F:80])[CH:74]=1)[C@H:59]([OH:71])[CH2:60][NH:61][C:62]1([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[CH2:64][CH2:63]1>C(OCC)(=O)C.O1CCCC1.CO.O>[ClH:55].[ClH:55].[CH2:1]([N:5]([CH2:7][C:8]1[CH:9]=[C:10]([CH:15]=[C:16]([CH3:18])[CH:17]=1)[C:11]([NH:57][C@@H:58]([CH2:72][C:73]1[CH:74]=[C:75]([F:80])[CH:76]=[C:77]([F:79])[CH:78]=1)[C@H:59]([OH:71])[CH2:60][NH:61][C:62]1([C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=2)[CH2:64][CH2:63]1)=[O:13])[CH3:6])[CH2:2][CH2:3][CH3:4]

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21086167Methyl 3-{[butyl(methyl)amino]methyl}-5-methylbenzoateHCID 57487337(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1-phenylcyclopropyl)amino]butan-2-ol dihydrochloride

생성물 1

HCID 686079873-{[Butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(1-phenylcyclopropyl)amino]propyl}-5-methylbenzamide Dihydrochloride

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

Analogous to the method in EXAMPLE SP-188, methyl 3-{[butyl(methyl)amino]methyl}-5-methylbenzoate (170 mg, 0.68 mmol) is dissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL), and lithium hydroxide monohydrate is added (57 mg, 1.4 mmol), and the reaction stirred 2 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (3 mL), and diisopropylethylamine (472 μL, 2.7 mmol), HATU (322 mg, 0.85 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(1-phenylcyclopropyl)amino]butan-2-ol dihydrochloride prepared by the method in EXAMPLE S-XYZ (275 mg, 0.68 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, brine, 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. EST MS m/z 550.3 [M+H]+.

후처리

  1. additionis added (57 mg, 1.4 mmol)
  2. concentrationThe solution is concentrated under reduced pressure
  3. dissolutionThe residue is redissolved in DMF (3 mL)
  4. additionare added
  5. stirringThe reaction stirred at room temperature 16 h
  6. washwashed with water, saturated sodium bicarbonate, brine
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, 8% methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-0d8d9fa92b964523807f592762812841
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176242B2

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