1,2-Dichloroethane → 3-{[[2-(Diethylamino)ethyl](methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Trihydrochloride

HRID 348922

Reaction equation

HRID 348922 reaction equation
[CH2:1]([N:3]([CH2:19][CH3:20])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([CH3:18])[CH:17]=1)[C:12]([OH:14])=O)[CH3:7])[CH3:2].[NH2:21][C@@H:22]([CH2:36][C:37]1[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=1)[C@H:23]([OH:35])[CH2:24][NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH2:33][CH3:34])[CH:28]=1.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.C(Cl)C[Cl:66]>C(Cl)Cl>[ClH:66].[ClH:66].[ClH:66].[CH2:19]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([CH3:18])[CH:17]=1)[C:12]([NH:21][C@@H:22]([CH2:36][C:37]1[CH:38]=[C:39]([F:44])[CH:40]=[C:41]([F:43])[CH:42]=1)[C@H:23]([OH:35])[CH2:24][NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH2:33][CH3:34])[CH:28]=1)=[O:14])[CH3:7])[CH3:20]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 210856653-{[[2-(Diethylamino)ethyl](methyl)amino]methyl}-5-methylbenzoic AcidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 686108923-{[[2-(Diethylamino)ethyl](methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Trihydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-{[[2-(diethylamino)ethyl](methyl)amino]methyl}-5-methylbenzoic acid (267 mg, 0.959 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of EXAMPLE SP-272 (391 mg, 0.959 mmol), HOBt (129 mg, 0.959 mmol), and N,N-diisopropylethylamine (496 mg, 3.84 mmol) in methylene chloride (5 mL) is added EDC (331 mg, 1.73 mmol). The reaction mixture is stirred overnight and then partitioned between ethyl acetate and water. The organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9:1:1 methylene chloride/methanol/ammonium hydroxide) gives the title compound. ESI MS m/z 595.4 [M+H]+.

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 9:1:1 methylene chloride/methanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-23987db5331d4f5694e56b4f945afb2c
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Linked notes

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