1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → [(1S)-2-(3,5-Dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[(2-tert-butoxy-2-oxo-1-phenyl-ethyl)sulfamoyl]benzoate

HRID 1529535Notes

Reaction equation

HRID 1529535 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH:7]([NH:14][S:15]([C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([OH:23])=[O:22])(=[O:17])=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:28][C:29]1[CH:30]=[N+:31]([O-:49])[CH:32]=[C:33]([Cl:48])[C:34]=1[CH2:35][C@@H:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([O:46][CH3:47])[CH:39]=1)O.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[C:1]([O:5][C:6](=[O:27])[CH:7]([NH:14][S:15]([C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([O:23][C@H:36]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([O:46][CH3:47])[CH:39]=1)[CH2:35][C:34]1[C:33]([Cl:48])=[CH:32][N+:31]([O-:49])=[CH:30][C:29]=1[Cl:28])=[O:22])(=[O:17])=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 71092494(S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 867206943-[(2-tert-Butoxy-2-oxo-1-phenyl-ethyl)sulfamoyl]benzoic acid

Product 1

HCID 86720695[(1S)-2-(3,5-Dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[(2-tert-butoxy-2-oxo-1-phenyl-ethyl)sulfamoyl]benzoateYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-[(2-tert-Butoxy-2-oxo-1-phenyl-ethyl)sulfamoyl]benzoic acid (1.216 g, 3.11 mmol) was added to a stirred suspension of (S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxide (1.07 g, 3.11 mmol) in N,N-dimethylformamide (12 mL). To the resultant solution was added N,N-4-(dimethylamino)pyridine (0.189 g, 1.55 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.192 g, 6.22 mmol) and the reaction was stirred at room temperature for 18 hours. After this time, the reaction mixture was concentrated under reduced pressure and water (30 mL) was added; the resulting off-white precipitate was filtered and dried in air. The crude material was purified over a 50 g silica cartridge on an ISOLERA system; eluting initially with iso-hexane with an increasing solvent gradient to 100% ethyl acetate over four column volumes, after which 100% ethyl acetate was maintained for six column volumes. The desired fractions were combined and concentrated under reduced pressure to yield the title product as a white solid (1.340 g, 60%).

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated under reduced pressure and water (30 mL)
  2. additionwas added
  3. filtrationthe resulting off-white precipitate was filtered
  4. customdried in air
  5. customThe crude material was purified over a 50 g silica cartridge on an ISOLERA system
  6. washeluting initially with iso-hexane with an increasing solvent gradient to 100% ethyl acetate over four column volumes
  7. temperatureafter which 100% ethyl acetate was maintained for six column volumes
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d2910248931b480499a0b74a78a9b5ae
Source dataset
uspto-grants-2015_07
Patent number
US09090606B2

Reaction notes

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