1,2-Dichloroethane → N-(4-((2R)-4-(4-(2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenyl sulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamide

HRID 1771233ノート

反応式

HRID 1771233 の反応式
[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.[Si:31]([O:48][C@@H:49]([CH2:86][F:87])[CH2:50][N:51]1[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][C@@H:59]([NH:68][C:69]2[CH:74]=[CH:73][C:72]([S:75]([NH2:78])(=[O:77])=[O:76])=[CH:71][C:70]=2[S:79]([C:82]([F:85])([F:84])[F:83])(=[O:81])=[O:80])[CH2:60][S:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:53][CH2:52]1)([C:44]([CH3:47])([CH3:46])[CH3:45])([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[Si](O[C@H](CF)CN1CCN(CC[C@@H](NC2C=CC(S(N)(=O)=O)=CC=2S(C(F)(F)F)(=O)=O)CSC2C=CC=CC=2)CC1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(Cl)CCl>CN(C1C=CN=CC=1)C>[Si:31]([O:48][CH:49]([CH2:86][F:87])[CH2:50][N:51]1[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][C@@H:59]([NH:68][C:69]2[CH:74]=[CH:73][C:72]([S:75]([NH:78][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:21]([N:18]4[CH2:19][CH2:20][CH:15]([C@H:14]([C:9]5[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=5[C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=5)[OH:30])[CH2:16][CH2:17]4)=[CH:22][CH:23]=3)(=[O:77])=[O:76])=[CH:71][C:70]=2[S:79]([C:82]([F:84])([F:83])[F:85])(=[O:80])=[O:81])[CH2:60][S:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH2:53][CH2:52]1)([C:44]([CH3:45])([CH3:46])[CH3:47])([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 58080224(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid2 回HCID 667238514-((R)-4-(4-((R)-2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideHCID 667238814-((R)-4-(4-((S)-2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

生成物 1

HCID 86661885N-(4-((2R)-4-(4-(2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenyl sulfonyl)-4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamide

試薬・触媒・溶媒 1

HCID 142844-(Dimethylamino)pyridine触媒

実験手順

(R)-4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 40, 58 mg, 0.14 mmol), 4-((R)-4-(4-((R)-2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide and 4-((R)-4-(4-((S)-2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide mixture of diastereomers (INTERMEDIATE 39, 120 mg, 0.14 mmol), DMAP (34 mg, 0.28 mmol), and EDC (53 mg, 0.28 mmol) were placed in a 40 ml vial and flushed with nitrogen. DCM (2.8 ml) was added, and the solution was stirred at room temperature overnight. The reaction mixture was diluted with DCM and washed with 1N aq. sodium bisulfate followed by a saturated aq. sodium bicarbonate. The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to give N-(4-((2R)-4-(4-(2-(tert-butyldiphenylsilyloxy)-3-fluoropropyl)piperazin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)-4-(4-((R)-(4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzamide (EXAMPLE 6, STEP 1, 180 mg), which was used in the preparation of EXAMPLE 6, STEP 2, without further purification.

後処理

  1. customflushed with nitrogen
  2. additionDCM (2.8 ml) was added
  3. additionThe reaction mixture was diluted with DCM
  4. washwashed with 1N aq. sodium bisulfate
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-41ef8ac94f904f878263da9e36151a67
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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