1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-(azetidin-1-ylsulfonyl)-4-{[(5-chloro-6-isopropoxypyridin-3-yl)oxy]methyl}-2,5-difluorobenzamide

HRID 1525652Notes

Reaction equation

HRID 1525652 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:12][CH2:13][C:14]2[C:22]([F:23])=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([F:24])[CH:15]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].Cl.CN(C)CCCN=C=NCC.[N:37]1([S:41]([NH2:44])(=[O:43])=[O:42])[CH2:40][CH2:39][CH2:38]1>ClCCl.CN(C)C1C=CN=CC=1.CS(C)=O>[N:37]1([S:41]([NH:44][C:18](=[O:20])[C:17]2[CH:21]=[C:22]([F:23])[C:14]([CH2:13][O:12][C:4]3[CH:5]=[N:6][C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[C:2]([Cl:1])[CH:3]=3)=[CH:15][C:16]=2[F:24])(=[O:43])=[O:42])[CH2:40][CH2:39][CH2:38]1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 450805661-AzetidinesulfonamideHCID 896192574-{[(5-Chloro-6-isopropoxypyridin-3-yl)oxy]methyl}-2,5-difluorobenzoic acid

Product 1

HCID 71616149N-(azetidin-1-ylsulfonyl)-4-{[(5-chloro-6-isopropoxypyridin-3-yl)oxy]methyl}-2,5-difluorobenzamideYield 20.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{[(5-chloro-6-isopropoxypyridin-3-yl)oxy]methyl}-2,5-difluorobenzoic acid (Preparation 15, 100 mg, 0.28 mmol) in dichloromethane (3 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (80 mg, 0.42 mmol) and 4-dimethylaminopyridine (51 mg, 0.42 mmol). The reaction was allowed to stir at room temperature for 20 minutes, before the addition of azetidine-1-sulfonamide (Preparation 19, 57 mg, 0.42 mmol). The reaction was stirred at room temperature for 18 hours. The solvent was removed in vacuo to leave a yellow solid. The crude material was dissolved in dimethylsulphoxide (2 mL) and purified twice by preparative HPLC to afford the title compound as a white powder (27 mg, 13%).

Workup

  1. customThe solvent was removed in vacuo
  2. customto leave a yellow solid
  3. custompurified twice by preparative HPLC

Sources & evidence

ORD record
ord-92b459fd9e1e442e89dc3161b6c03838
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Reaction notes

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