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

HRID 348939ノート

反応式

HRID 348939 の反応式
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][C:10]1[CH:11]=[C:12]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[C:13]([OH:15])=O.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.[NH2:63][C@@H:64]([CH2:78][C:79]1[CH:84]=[C:83]([F:85])[CH:82]=[C:81]([F:86])[CH:80]=1)[C@H:65]([OH:77])[CH2:66][NH:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[C:71]([CH2:75][CH3:76])[CH:70]=1.[ClH:87]>C(Cl)Cl.CO.C(OCC)C>[ClH:87].[ClH:87].[F:85][C:83]1[CH:84]=[C:79]([CH:80]=[C:81]([F:86])[CH:82]=1)[CH2:78][C@H:64]([NH:63][C:13](=[O:15])[C:12]1[CH:16]=[C:17]([CH3:19])[CH:18]=[C:10]([CH2:9][N:5]2[CH2:6][CH2:7][CH2:8][C@H:4]2[CH2:3][O:2][CH3:1])[CH:11]=1)[C@H:65]([OH:77])[CH2:66][NH:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[C:71]([CH2:75][CH3:76])[CH:70]=1

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 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-olHCID 574873683-{[(2S)-2-(Methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoic Acid

生成物 1

HCID 68609540N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-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-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoic acid (110 mg, 0.42 mmol) in methylene chloride (3 mL) is added HBTU (240 mg, 0.63 mmol), HOBt (85 mg, 0.63 mmol), and N,N-diisopropylethylamine (0.212 mL, 1.26 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 (171 mg, 0.42 mmol). 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 was collected by filtration to provide the title compound. ESI MS m/z 580.4 [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. filtrationwas collected by filtration

出典と根拠

ORDレコード
ord-2f53464d6f4c4de2aa01e649e0bfa1a2
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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