1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide

HRID 59737ノート

反応式

HRID 59737 の反応式
[CH3:1][S:2]([NH:5][C:6]1[CH:10]=[CH:9][S:8][C:7]=1[C:11]([OH:13])=[O:12])(=[O:4])=[O:3].[Cl:14][C:15]1[CH:16]=[N+:17]([O-:40])[CH:18]=[C:19]([Cl:39])[C:20]=1[CH2:21][C@@H:22]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH:31]([F:33])[F:32])=[C:26]([O:34][CH2:35][CH:36]2[CH2:38][CH2:37]2)[CH:25]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:14][C:15]1[CH:16]=[N+:17]([O-:40])[CH:18]=[C:19]([Cl:39])[C:20]=1[CH2:21][C@@H:22]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH:31]([F:33])[F:32])=[C:26]([O:34][CH2:35][CH:36]2[CH2:38][CH2:37]2)[CH:25]=1)[O:12][C:11]([C:7]1[S:8][CH:9]=[CH:10][C:6]=1[NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[O:13]

参加物

6

反応物 3

HCID 111,2-DichloroethaneHCID 167739453-Methanesulfonamidothiophene-2-carboxylic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

生成物 1

HCID 72706758(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide収率 30.6%

試薬・触媒・溶媒 2

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

実験手順

A mixture of 3-(methylsulfonamido)thiophene-2-carboxylic acid (Int. 38) (110 mg, 0.497 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (209 mg, 0.497 mmol), EDC (286 mg, 1.491 mmol) and DMAP (30.4 mg, 0.249 mmol) in DCM (25 ml) was stirred at RT for 3 days. The mixture was diluted with DCM and washed with 1N HCl and aqueous NaHCO3; the organic layer was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel cartridge (DCM/MeOH=99.5/0.5 to 99/1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide (Int. 39) (95 mg, 0.152 mmol, MS/ESI+623.05 [MH]+, [αD]=−28.6, c=0.3, DCM).

後処理

  1. washwashed with 1N HCl and aqueous NaHCO3
  2. dry with materialthe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude was purified by flash chromatography on silica gel cartridge (DCM/MeOH=99.5/0.5 to 99/1)

出典と根拠

ORDレコード
ord-242719a229a24142be1434d632b1633f
出典データセット
uspto-grants-2016_09
特許番号
US09440954B2

反応ノート

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