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

HRID 14104Notes

Reaction equation

HRID 14104 reaction equation
[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

Participants

7

Reactant 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)propylamino]methyl]benzoateHCID 57487297HCID 57487297, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

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]+.

Workup

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

Sources & evidence

ORD record
ord-6160bffc1c5a45c199e55ae957a40527
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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