1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(methylthio)-phenylamino)-3-oxopropanoyloxy)ethyl)pyridine 1-oxide

HRID 1776493ノート

反応式

HRID 1776493 の反応式
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[CH3:28][S:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:42])[CH2:38][C:39](O)=[O:40])=[CH:32][CH:31]=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:39](=[O:40])[CH2:38][C:37]([NH:36][C:33]1[CH:34]=[CH:35][C:30]([S:29][CH3:28])=[CH:31][CH:32]=1)=[O:42]

参加物

7

反応物 3

HCID 111,2-DichloroethaneHCID 622307273-(4-(Methylthio)phenylamino)-3-oxopropanoic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

生成物 1

HCID 71542175(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(methylthio)-phenylamino)-3-oxopropanoyloxy)ethyl)pyridine 1-oxide収率 44.9%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (30 mg, 0.071 mmol), 3-(4-(methylthio)-phenylamino)-3-oxopropanoic acid (32.2 mg, 0.143 mmol), DMAP (13.08 mg, 0.107 mmol), and EDC (41.1 mg, 0.214 mmol) were dissolved in DMF (1.5 ml). The reaction was stirred at RT overnight. The reaction mixture was diluted with water and extracted with EtOAc. The organic phase was washed with HCl 1N, Na2CO3 sat. sol. and brine, dried over Na2SO4 and concentrated under vacuum. The crude product was purified by preparative reverse-phase HPLC to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(4-(methylthio)-phenylamino)-3-oxopropanoyloxy)ethyl)pyridine 1-oxide (20 mg, 44.6% yield).

後処理

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with HCl 1N, Na2CO3 sat. sol. and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by preparative reverse-phase HPLC

出典と根拠

ORDレコード
ord-d319ef9a1ed648f1ab2f3af354a291f7
出典データセット
uspto-grants-2016_02
特許番号
US09265768B2

反応ノート

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