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

HRID 14104노트

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HRID 14104 반응식
[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

참가 물질

7

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 21086147Methyl 3-{[(2-hydroxyethyl)(propyl)amino]methyl}benzoateHCID 57487297HCID 57487297, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

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]+.

후처리

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

출처 및 근거

ORD 기록
ord-6160bffc1c5a45c199e55ae957a40527
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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