1,2-Dichloroethane → (S)-4-(2-(3-(N-(tert-butoxycarbonyl)-N-methylsulfamoyl)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy) phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 59735노트

반응식

HRID 59735 반응식
[C:1]([O:5][C:6]([N:8]([CH3:20])[S:9]([C:12]1[CH:16]=[CH:15][S:14][C:13]=1[C:17]([OH:19])=[O:18])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([CH3:20])[S:9]([C:12]1[CH:16]=[CH:15][S:14][C:13]=1[C:17]([O:19][C@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:39])[F:40])=[C:33]([O:41][CH2:42][CH:43]2[CH2:44][CH2:45]2)[CH:32]=1)[CH2:28][C:27]1[C:26]([Cl:46])=[CH:25][N+:24]([O-:47])=[CH:23][C:22]=1[Cl:21])=[O:18])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 867038413-(N-(tert-butoxycarbonyl)-N-methylsulfamoyl)-thiophene-2-carboxylic acid

생성물 1

HCID 86703840(S)-4-(2-(3-(N-(tert-butoxycarbonyl)-N-methylsulfamoyl)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy) phenyl)ethyl)-3,5-dichloropyridine 1-oxide수율 68.1%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-(N-(tert-butoxycarbonyl)-N-methylsulfamoyl)-thiophene-2-carboxylic acid (Int. 34) (150 mg, 0.467 mmol) in DCM (5 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (196 mg, 0.467 mmol), EDC (268 mg, 1.400 mmol) and DMAP (28.5 mg, 0.233 mmol) were added and the mixture was reacted at RT overnight. The solvent was removed and the crude was purified by flash chromatography on silica gel (DCM/MeOH=95/5) affording (S)-4-(2-(3-(N-(tert-butoxycarbonyl)-N-methylsulfamoyl)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy) phenyl)ethyl)-3,5-dichloropyridine 1-oxide (Int. 35) (230 mg, 0.318 mmol, MS/ESI+722.8 [MH]+).

후처리

  1. customthe mixture was reacted at RT overnight
  2. customThe solvent was removed
  3. customthe crude was purified by flash chromatography on silica gel (DCM/MeOH=95/5)

출처 및 근거

ORD 기록
ord-fac8cad567ae4fadbbb965903be22373
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440954B2

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