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

HRID 1776481
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HRID 1776481 반응식
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[C:10]([SH:12])[CH:9]=[CH:8][C:7]=2[NH:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:3][CH2:2]1.[Cl:18][C:19]1[CH:20]=[N+:21]([O-:56])[CH:22]=[C:23]([Cl:55])[C:24]=1[CH2:25][C@@H:26]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)[O:27][C:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:55][C:23]1[CH:22]=[N+:21]([O-:56])[CH:20]=[C:19]([Cl:18])[C:24]=1[CH2:25][C@@H:26]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)[O:27][C:28]([S:12][C:10]1[CH:9]=[CH:8][C:7]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[CH:11]=1)=[O:29]
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참가 물질

5

반응물 2

HCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxideHCID 86679432N-(2-(cyclopropylmethoxy)-4-mercaptophenyl)methanesulfonamide

생성물 1

HCID 71542824(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((3-(cyclopropylmethoxy)-4-(methylsulfonamido)-phenylthio)carbonyloxy)ethyl)pyridine 1-oxide

시약·촉매·용매 2

HCID 14284
4-(Dimethylamino)pyridine
촉매
HCID 6344Dichloromethane용매2회

실험 절차

A solution of N-(2-(cyclopropylmethoxy)-4-mercaptophenyl)-methanesulfonamide (0.112 g, 0.410 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide (prepared with an analogous procedure to that described in Scheme 3, Step 1) (0.200 g, 0.342 mmol), and DMAP (0.021 g, 0.171 mmol) in DCM (8 ml) was stirred at RT overnight. The mixture was diluted with DCM and washed several times with diluted aqueous K2CO3. The organic layer was dried over Na2SO4 and the solvent was removed. The crude was purified by filtration on silica gel cartridge (DCM:EtOAc=80:20) affording the desired compound as a pale yellow amorphous solid. The product was further purified by flash chromatography on silica gel cartridge (petroleum ether:EtOAc=50:50 to 35:65) and by preparative LC/MS affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((3-(cyclopropylmethoxy)-4-(methylsulfonamido)phenylthio)carbonyloxy)ethyl)pyridine 1-oxide as an off-white amorphous solid (0.060 g, 0.083 mmol, 24.40% yield, MS/ESI+ 719.23 [MH]+, [αD]=−64.64, c=0.47 in DCM).

후처리

  1. washwashed several times with diluted aqueous K2CO3
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was removed
  4. filtrationThe crude was purified by filtration on silica gel cartridge (DCM:EtOAc=80:20)

출처 및 근거

ORD 기록
ord-f31d73e329ac4591b44318a2ddc6ef6f
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09265768B2

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