Diisopropylethylamine → 5-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]methyl}-N-[(3,3-difluoroazetidin-1-yl)sulfonyl]-2-fluorobenzamide

HRID 1525655Notes

Reaction equation

HRID 1525655 reaction equation
[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[F:24][C:25]1([F:33])[CH2:28][N:27]([S:29]([NH2:32])(=[O:31])=[O:30])[CH2:26]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:32][S:29]([N:27]1[CH2:28][C:25]([F:33])([F:24])[CH2:26]1)(=[O:31])=[O:30])=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 672167873,3-Difluoroazetidine-1-sulfonamideHCID 896191735-Chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acidHCID 178484293HCID 178484293, compound

Product 1

HCID 716162675-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]methyl}-N-[(3,3-difluoroazetidin-1-yl)sulfonyl]-2-fluorobenzamideYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acid (Preparation 27, 100 mg, 0.28 mmol) and 3,3-difluoroazetidine-1-sulfonamide (Preparation 23, 75 mg, 0.42 mmol) in DCM (10 mL) was added diisopropylethylamine (73 mg, 0.56 mmol) followed by 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (160 mg, 0.42 mmol). The mixture was stirred at room temperature for 2 hours and concentrated under reduced pressure. The residue was dissolved in DMSO (2 mL) and purified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid) to give the title compound as colourless solid (51 mg, 36%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DMSO (2 mL)
  3. custompurified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid)

Sources & evidence

ORD record
ord-6f7d66124e9c40599abaddc8cf7ea588
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Reaction notes

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