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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 14130
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HRID 14130 반응식
[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]
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참가 물질

7

반응물 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

생성물 1

HCID 68610892
3-{[[2-(Diethylamino)ethyl](methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Trihydrochloride

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-74d9a4777c80413db2aabea8dbe422b7
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07727997B2

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