1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(5-(N-(4-(dimethylcarbamoyl)phenyl)-sulfamoyl)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide

HRID 59760Notes

Reaction equation

HRID 59760 reaction equation
[CH3:1][N:2]([CH3:23])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([C:15]2[S:19][C:18]([C:20]([OH:22])=[O:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:7][CH:6]=1)=[O:4].C(Cl)CCl.[Cl:28][C:29]1[CH:30]=[N+:31]([O-:54])[CH:32]=[C:33]([Cl:53])[C:34]=1[CH2:35][C@@H:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH:45]([F:47])[F:46])=[C:40]([O:48][CH2:49][CH:50]2[CH2:52][CH2:51]2)[CH:39]=1)O>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:28][C:29]1[CH:30]=[N+:31]([O-:54])[CH:32]=[C:33]([Cl:53])[C:34]=1[CH2:35][C@@H:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH:45]([F:47])[F:46])=[C:40]([O:48][CH2:49][CH:50]2[CH2:52][CH2:51]2)[CH:39]=1)[O:21][C:20]([C:18]1[S:19][C:15]([S:12](=[O:14])(=[O:13])[NH:11][C:8]2[CH:9]=[CH:10][C:5]([C:3](=[O:4])[N:2]([CH3:23])[CH3:1])=[CH:6][CH:7]=2)=[CH:16][CH:17]=1)=[O:22]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 867038655-(N-(4-(dimethylcarbamoyl)phenyl)sulfamoyl)thiophene-2-carboxylic acid

Product 1

HCID 72706890(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(5-(N-(4-(dimethylcarbamoyl)phenyl)-sulfamoyl)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxideYield 13%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-(N-(4-(dimethylcarbamoyl)phenyl)sulfamoyl)thiophene-2-carboxylic acid (Int. 76) (54 mg, 0.152 mmol), DMAP (6.20 mg, 0.051 mmol), and EDC (38.9 mg, 0.203 mmol) were dissolved in DMF. (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (42.7 mg, 0.102 mmol) was added. The reaction was stirred at RT for 4 hours. The reaction mixture was diluted with water and extracted with AcOEt. The organic phase was dried over Na2SO4 and concentrated under vacuum to give a crude product which was purified by preparative HPLC-Method 2 to give 10 mg of the desired product (Compound 77).

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customto give a crude product which
  5. customwas purified by preparative HPLC-Method 2

Sources & evidence

ORD record
ord-d1bb2cf791904e1cbb8bcf0039712f40
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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