Hydrochloric Acid → 3-[(Butylamino)methyl]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Dihydrochloride

HRID 348936ノート

反応式

HRID 348936 の反応式
C(OC([N:8]([CH2:13][C:14]1[CH:15]=[C:16]([CH:20]=[C:21]([CH3:23])[CH:22]=1)[C:17]([OH:19])=O)[CH2:9][CH2:10][CH2:11][CH3:12])=O)(C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[NH2:67][C@@H:68]([CH2:82][C:83]1[CH:88]=[C:87]([F:89])[CH:86]=[C:85]([F:90])[CH:84]=1)[C@H:69]([OH:81])[CH2:70][NH:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[C:75]([CH2:79][CH3:80])[CH:74]=1.[ClH:91]>C(Cl)Cl.CO.C(OCC)C>[ClH:91].[ClH:91].[CH2:9]([NH:8][CH2:13][C:14]1[CH:15]=[C:16]([CH:20]=[C:21]([CH3:23])[CH:22]=1)[C:17]([NH:67][C@@H:68]([CH2:82][C:83]1[CH:84]=[C:85]([F:90])[CH:86]=[C:87]([F:89])[CH:88]=1)[C@H:69]([OH:81])[CH2:70][NH:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[C:75]([CH2:79][CH3:80])[CH:74]=1)=[O:19])[CH2:10][CH2:11][CH3:12]

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210858673-{[(tert-Butoxycarbonyl)(butyl)amino]methyl}-5-methylbenzoic AcidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

生成物 1

HCID 686098413-[(Butylamino)methyl]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Dihydrochloride

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred solution of 3-{[(tert-butoxycarbonyl)(butyl)amino]methyl}-5-methylbenzoic acid (90 mg, 0.28 mmol) in methylene chloride (3 mL) is added HBTU (160 mg, 0.42 mmol), HOBt (57 mg, 0.42 mmol), and N,N-diisopropylethylamine (0.142 mL, 0.84 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of EXAMPLE SP-272 (114 mg, 0.28 mmol), and the reaction mixture is stirred for 12 h at room temperature. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 10% methanol/chloroform) affords a clear oil, which is dissolved in methanol (2 mL). To this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol), and the reaction mixture is stirred for 1 h at room temperature. The reaction mixture is then diluted with ethyl ether (10 mL). The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 538.5 [M+H]+.

後処理

  1. washwashed with water, and saturated sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 10% methanol/chloroform)
  6. customaffords a clear oil, which
  7. stirringthe reaction mixture is stirred for 1 h at room temperature
  8. customThe precipitate that is formed
  9. filtrationis collected by filtration

出典と根拠

ORDレコード
ord-0cf2d0a9fec047f48089ec1cd632788c
出典データセット
uspto-grants-2007_02
特許番号
US07176242B2

反応ノート

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