Diisopropylethylamine → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzamide Dihydrochloride

HRID 348896ノート

反応式

HRID 348896 の反応式
[OH:1][CH2:2][CH2:3][N:4]([CH2:8][C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([O:14]C)=O)[CH2:5][CH2:6][CH3:7].O.[OH-].[Li+].[ClH:22].Cl.[NH2:24][C@@H:25]([CH2:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)[C@H:26]([OH:37])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([I:36])[CH:31]=1.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>O1CCCC1.CO.O>[ClH:22].[ClH:22].[F:45][C:43]1[CH:44]=[C:39]([CH:40]=[C:41]([F:46])[CH:42]=1)[CH2:38][C@H:25]([NH:24][C:12](=[O:14])[C:11]1[CH:16]=[CH:17][CH:18]=[C:9]([CH2:8][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6][CH3:7])[CH:10]=1)[C@H:26]([OH:37])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([I:36])[CH:31]=1

参加物

7

反応物 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 21086147Methyl 3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzoateHCID 57487297HCID 57487297、化合物

生成物 1

HCID 68608663N-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-iodobenzyl)amino]propyl}-3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzamide Dihydrochloride

試薬・触媒・溶媒 1

HCID 21892291Methanol tetrahydrofuran water溶媒

実験手順

Methyl 3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzoate (500 mg, 2 mmol) and lithium hydroxide monohydrate (170 mg, 4 mmol) are stirred in 2:1:1 tetrahydrofuran/methanol/water (4 mL) at room temperature for 16 h. The reaction is concentrated under reduced pressure and redissolved in DMF (15 mL). To this solution is added (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-iodobenzyl)amino]butan-2-ol dihydrochloride (1 g, 2 mmol), diisopropylethylamine (1.4 mL, 8 mmol), then HATU (1.1 g, 3 mmol), and the reaction stirred 2 h. Purification by flash column chromatography (silica, 10% methanol/chloroform) provides the title compound as the free base. The residue is dissolved in diethyl ether (5 mL) and 1N hydrochloric acid in diethyl ether (3 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 652.2 [M+H]+.

後処理

  1. concentrationThe reaction is concentrated under reduced pressure
  2. dissolutionredissolved in DMF (15 mL)
  3. customPurification by flash column chromatography (silica, 10% methanol/chloroform)

出典と根拠

ORDレコード
ord-53a61d60974346d4a5637e1106704198
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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