1,2-Dichloroethane → Di-tert-butyl 2-(((R)-3-(4-(N-(4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)(ethyl)amino)ethyl phosphate

HRID 1476292노트

반응식

HRID 1476292 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([OH:30])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.C(Cl)CCl.C(N(CC)CC)C.[P:42]([O:54][CH2:55][CH2:56][N:57]([CH2:87][CH3:88])[CH2:58][CH2:59][C@@H:60]([NH:69][C:70]1[CH:75]=[CH:74][C:73]([S:76](=[O:79])(=[O:78])[NH2:77])=[CH:72][C:71]=1[S:80]([C:83]([F:86])([F:85])[F:84])(=[O:82])=[O:81])[CH2:61][S:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[P:42]([O:54][CH2:55][CH2:56][N:57]([CH2:58][CH2:59][C@@H:60]([NH:69][C:70]1[CH:75]=[CH:74][C:73]([S:76](=[O:79])(=[O:78])[NH:77][C:25](=[O:26])[C:24]2[CH:28]=[CH:29][C:21]([N:18]3[CH2:19][CH2:20][CH:15]([C@H:14]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[OH:30])[CH2:16][CH2:17]3)=[CH:22][CH:23]=2)=[CH:72][C:71]=1[S:80]([C:83]([F:85])([F:86])[F:84])(=[O:82])=[O:81])[CH2:61][S:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH2:87][CH3:88])([O:44][C:45]([CH3:46])([CH3:48])[CH3:47])([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:43]

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 58080224(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid2회HCID 66723800(R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate2회

생성물 1

HCID 87125282Di-tert-butyl 2-(((R)-3-(4-(N-(4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)(ethyl)amino)ethyl phosphate수율 59.5%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (R)-4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 40, 88 mg, 0.20 mmol), EDC (77 mg, 0.40 mmol), and DMAP (49 mg, 0.40 mmol), triethylamine (28 μl, 0.20 mmol) in 5 ml of DCM was added (R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate (INTERMEDIATE 50, 150 mg, 0.20 mmol). The mixture was stirred at r.t overnight. The reaction solution was diluted with DCM (20 ml) and washed with water (30 ml). The aqueous layer was extracted with DCM (30 ml) and the combined organic layers were dried over sodium sulfate, and concentrated in vacuo to an oil. This material was purified by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc) to provide the title compound (137 mg, yield: 59%).

후처리

  1. washwashed with water (30 ml)
  2. extractionThe aqueous layer was extracted with DCM (30 ml)
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated in vacuo to an oil
  5. customThis material was purified by column chromatography (ISCO, 0→100% EtOAc/hexane followed by 0→10% MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-0b4ad407e19b45799c4e8904492d82e5
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018381B2

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