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1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N,N-dimethylsulfamoyl)-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571270
ノート
印刷プレビュー

反応式

HRID 571270 の反応式
[CH3:1][N:2]([CH3:21])[S:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([OH:18])=[O:17])[C:10](=[O:19])[C:9]2=[O:20])(=[O:5])=[O:4].[Cl:22][C:23]1[CH:24]=[N+:25]([O-:48])[CH:26]=[C:27]([Cl:47])[C:28]=1[CH2:29][C@@H:30]([C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:41])[F:40])=[C:34]([O:42][CH2:43][CH:44]2[CH2:46][CH2:45]2)[CH:33]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:22][C:23]1[CH:24]=[N+:25]([O-:48])[CH:26]=[C:27]([Cl:47])[C:28]=1[CH2:29][C@@H:30]([C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:41])[F:40])=[C:34]([O:42][CH2:43][CH:44]2[CH2:46][CH2:45]2)[CH:33]=1)[O:17][C:16](=[O:18])[CH2:15][N:11]1[C:12]2[C:8](=[CH:7][C:6]([S:3](=[O:5])(=[O:4])[N:2]([CH3:21])[CH3:1])=[CH:14][CH:13]=2)[C:9](=[O:20])[C:10]1=[O:19]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 866816832-(5-(N,N-dimethylsulfamoyl)-2,3-dioxoindolin-1-yl)acetic acid

生成物 1

HCID 86681684(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N,N-dimethylsulfamoyl)-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide収率 37.6%

試薬・触媒・溶媒 2

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

実験手順

A mixture of crude 2-(5-(N,N-dimethylsulfamoyl)-2,3-dioxoindolin-1-yl)acetic acid (0.178 g, 0.57 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.200 g, 0.476 mmol), EDC (0.274 g, 1.428 mmol) and DMAP (0.029 g, 0.238 mmol) in dry DCM (10 ml) was stirred at room temperature overnight. The mixture was washed with 1N HCl, aqueous 5% NaHCO3 and brine. The organic layer was dried over sodium sulfate and concentrated under vacuum. The crude was purified by silica gel flash chromatography (DCM:MeOH from 99.5:0.5 to 98:2) to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N,N-dimethylsulfamoyl)-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.128 g, 0.179 mmol, 37% yield). This product was further purified by crystallization from ethyl acetate/hexane 1/1 to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N,N-dimethyl sulfamoyl)-2,3-dioxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.052 g, 0.179 mmol, 15% yield). MS/ESI+ 714.11 [MH]+; [αD]=−37.09, c=0.488; MeOH; 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.15 (s, 2H), 8.06 (d, 1H), 8.00 (dd, 1H), 7.19 (d, 1H), 6.83-7.01 (m, 2H), 6.74 (d, 1H), 6.67 (t, 1H), 6.13 (dd, 1H), 4.53 (d, 2H), 3.91 (d, 2H), 3.58 (dd, 1H), 3.28 (dd, 1H), 2.79 (s, 6H), 1.09-1.43 (m, 1H), 0.55-0.84 (m, 2H), 0.18-0.52 (m, 2H)

後処理

  1. washThe mixture was washed with 1N HCl, aqueous 5% NaHCO3 and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe crude was purified by silica gel flash chromatography (DCM:MeOH from 99.5:0.5 to 98:2)

出典と根拠

ORDレコード
ord-2f7e3b0a4554461c8103620e325ab0b4
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09024027B2

反応ノート

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