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

HRID 1771194노트

반응식

HRID 1771194 반응식
[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[C:29](Cl)[CH:28]=[CH:27][C:26]=1[C:32]1[CH:37]=CC=[CH:34][CH:33]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[P:38]([O:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][N:56]([CH2:59][CH2:60][C@@H:61]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([S:77](=[O:80])(=[O:79])[NH2:78])=[CH:73][C:72]=2[S:81]([C:84]([F:87])([F:86])[F:85])(=[O:83])=[O:82])[CH2:62][S:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[CH2:55][CH2:54]1)([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].[CH2:88]([Cl:91])[CH2:89]Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[P:38]([O:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][N:56]([CH2:59][CH2:60][C@@H:61]([NH:70][C:71]2[CH:76]=[CH:75][C:74]([S:77](=[O:79])(=[O:80])[NH:78][C:20](=[O:21])[C:19]3[CH:23]=[CH:24][C:16]([N:13]4[CH2:12][CH2:11][CH:10]([C@@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3])[C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[C:32]5[CH:37]=[CH:89][C:88]([Cl:91])=[CH:34][CH:33]=5)[CH2:15][CH2:14]4)=[CH:17][CH:18]=3)=[CH:73][C:72]=2[S:81]([C:84]([F:87])([F:86])[F:85])(=[O:83])=[O:82])[CH2:62][S:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[CH2:55][CH2:54]1)([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39]

참가 물질

6

반응물 3

HCID 111,2-DichloroethaneHCID 66723554(R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate2회HCID 66723720(R)-4-(4-((tert-butyldimethylsilyloxy)(4-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid2회

생성물 1

HCID 58080246Di-tert-butyl 2-(4-((R)-3-(4-(N-(4-(4-((R)-(tert-butyl dimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperazin-1-yl)ethyl phosphate

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

(R)-4-(4-((tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 13, 170 mg, 0.32 mmol), (R)-di-tert-butyl 2-(4-(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)piperazin-1-yl)ethyl phosphate (INTERMEDIATE 61, 275 mg, 0.35 mmol), DMAP (116 mg, 0.95 mmol) and EDC (122 mg, 0.63 mmol) were dissolved in DCM (3.2 ml). The reaction mixture was stirred at r.t. for 72 hours. The mixture was diluted with DCM (10 ml) and washed with NaHCO3 solution (saturated, aq., 5 ml) and brine (5 ml). The collected organic layer was dried over Na2SO4 and concentrated to give the title compound (446 mg, yield: almost quantitative). The title compound was used in the preparation of EXAMPLE 10 without further purification.

후처리

  1. washwashed with NaHCO3 solution (saturated, aq., 5 ml) and brine (5 ml)
  2. dry with materialThe collected organic layer was dried over Na2SO4
  3. concentrationconcentrated

출처 및 근거

ORD 기록
ord-4623c523e10f46bba503d2dbb278f35d
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09248140B2

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