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 59737노트

반응식

HRID 59737 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-242719a229a24142be1434d632b1633f
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440954B2

반응 노트

불러오는 중…