1,2-Dichloroethane → 3,5-Dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(((S)-3-((3-((2-(3-formylbenzamido)ethyl)carbamoyl)phenyl)sulfonyl)thiazolidine-2-carbonyl)oxy)ethyl)pyridine 1-oxide

HRID 520342Notes

Reaction equation

HRID 520342 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:9]=[C:10]([S:14]([N:17]2[CH2:21][CH2:20][S:19][C@H:18]2[C:22]([O:24][C@H:25]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:45])[F:44])=[C:38]([O:46][CH2:47][CH:48]3[CH2:50][CH2:49]3)[CH:37]=2)[CH2:26][C:27]2[C:32]([Cl:33])=[CH:31][N+:30]([O-:34])=[CH:29][C:28]=2[Cl:35])=[O:23])(=[O:16])=[O:15])[CH:11]=[CH:12][CH:13]=1)=[O:7].[CH:51]([C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[C:56](O)=[O:57])=[O:52].C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:35][C:28]1[CH:29]=[N+:30]([O-:34])[CH:31]=[C:32]([Cl:33])[C:27]=1[CH2:26][C@@H:25]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]2[CH2:50][CH2:49]2)[CH:37]=1)[O:24][C:22]([C@H:18]1[N:17]([S:14]([C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([C:6](=[O:7])[NH:5][CH2:4][CH2:3][NH:2][C:56](=[O:57])[C:55]3[CH:59]=[CH:60][CH:61]=[C:53]([CH:51]=[O:52])[CH:54]=3)[CH:9]=2)(=[O:15])=[O:16])[CH2:21][CH2:20][S:19]1)=[O:23]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 120773-CarboxybenzaldehydeHCID 1185584544-((S)-2-((S)-3-(3-(2-aminoethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide hydrochloride

Product 1

HCID 1185584603,5-Dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(((S)-3-((3-((2-(3-formylbenzamido)ethyl)carbamoyl)phenyl)sulfonyl)thiazolidine-2-carbonyl)oxy)ethyl)pyridine 1-oxideYield 45.9%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-((S)-2-((S)-3-(3-(2-Aminoethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide hydrochloride (195 mg, 0.244 mmol), 3-formylbenzoic acid (110 mg, 0.733 mmol), DMAP (5.97 mg, 0.049 mmol) and EDC (141 mg, 0.733 mmol) were dissolved in DMF. The reaction was stirred at RT overnight to achieve completion. The reaction mixture was diluted with water, and the precipitate was washed with water, dissolved in DCM and extracted with water. The organic phase was dried over Na2SO4 and concentrated under vacuum to give 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-(2-(3-formylbenzamido)ethylcarbamoyl)-phenylsulfonyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide (100 mg, 0.112 mmol, 45.8% yield).

Workup

  1. washthe precipitate was washed with water
  2. dissolutiondissolved in DCM
  3. extractionextracted with water
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-56a5924b83b740ac8648b9e1822171ca
Source dataset
uspto-grants-2016_05
Patent number
US09326976B2

Reaction notes

Loading…