1,2-Dichloroethane → 4-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1771212ノート

反応式

HRID 1771212 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]=[CH:36][CH:35]=[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]([OH:22])=O)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:38]([N:40]([CH2:43][C@@H:44]1[N:49]([CH2:50][CH2:51][C@@H:52]([NH:61][C:62]2[CH:67]=[CH:66][C:65]([S:68]([NH2:71])(=[O:70])=[O:69])=[CH:64][C:63]=2[S:72]([C:75]([F:78])([F:77])[F:76])(=[O:74])=[O:73])[CH2:53][S:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:48][CH2:47][O:46][CH2:45]1)[CH2:41][CH3:42])[CH3:39].C(Cl)C[Cl:81]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:1]([O:8][C@@H:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:32]1[CH:33]=[CH:34][C:35]([Cl:81])=[CH:36][CH:37]=1)[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([NH:71][S:68]([C:65]3[CH:66]=[CH:67][C:62]([NH:61][C@H:52]([CH2:51][CH2:50][N:49]4[CH2:48][CH2:47][O:46][CH2:45][C@@H:44]4[CH2:43][N:40]([CH2:41][CH3:42])[CH2:38][CH3:39])[CH2:53][S:54][C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)=[C:63]([S:72]([C:75]([F:76])([F:78])[F:77])(=[O:74])=[O:73])[CH:64]=3)(=[O:69])=[O:70])=[O:22])=[CH:23][CH:24]=2)[CH2:14][CH2:15]1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 111,2-DichloroethaneHCID 667234924-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2 回HCID 66723720(R)-4-(4-((tert-butyldimethylsilyloxy)(4-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid2 回

生成物 1

HCID 866618974-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide収率 43.2%

試薬・触媒・溶媒 2

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

実験手順

A solution of (R)-4-(4-((tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoic acid, (INTERMEDIATE 13, 109 mg, 0.20 mmol), 4-((R)-4-((S)-3-((diethylamino)methyl)morpholino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 88, 130 mg, 0.20 mmol), EDC (78 mg, 0.41 mmol), DMAP (49.7 mg, 0.41 mmol), TEA (0.028 ml, 0.20 mmol) and DCM (5 ml) was stirred overnight at room temperature. The reaction mixture was diluted with DCM (50 ml) and washed successively with water (2×50 ml) and brine (50 ml). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0-20 MeOH/DCM over 19 minutes) to give the title product (100 mg, yield: 42.5%).

後処理

  1. washwashed successively with water (2×50 ml) and brine (50 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe concentrate was purified by column chromatography (ISCO, eluting with 0-20 MeOH/DCM over 19 minutes)

出典と根拠

ORDレコード
ord-7737b1800bac4feca27bdafaeecce193
出典データセット
uspto-grants-2016_02
特許番号
US09248140B2

反応ノート

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