1,2-Dichloroethane → HCID 71542266, compound

HRID 1776496Notes

Reaction equation

HRID 1776496 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][O:29][C:30]1[CH:31]=[C:32]([NH:38][C:39](=[O:44])[CH2:40][C:41](O)=[O:42])[CH:33]=[CH:34][C:35]=1[O:36][CH3:37].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:41](=[O:42])[CH2:40][C:39]([NH:38][C:32]1[CH:33]=[CH:34][C:35]([O:36][CH3:37])=[C:30]([O:29][CH3:28])[CH:31]=1)=[O:44]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 55049108HCID 55049108, compoundHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 71542266HCID 71542266, compoundYield 43.9%

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-(3,4-dimethoxyphenylamino)-3-oxopropanoic acid (34.2 mg, 0.143 mmol), DMAP (17.44 mg, 0.143 mmol), and EDC (41.1 mg, 0.214 mmol) were dissolved in DMF (1.5 ml). The reaction was stirred at RT overnight to achieve completion. 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-(3,4-dimethoxyphenylamino)-3-oxopropanoyloxy)-ethyl)pyridine 1-oxide (20 mg, 43.7% 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-d813f0c5b9e14e9389ecbea6844924b3
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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