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 1771194ノート

反応式

HRID 1771194 の反応式
[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]

参加物

6

反応物 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 phosphate2 回HCID 66723720(R)-4-(4-((tert-butyldimethylsilyloxy)(4-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid2 回

生成物 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

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-4623c523e10f46bba503d2dbb278f35d
出典データセット
uspto-grants-2016_02
特許番号
US09248140B2

反応ノート

読み込み中…