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 1776493Notes

Reaction equation

HRID 1776493 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-d319ef9a1ed648f1ab2f3af354a291f7
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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