Cyclohexylamine → HCID 20505863, compound

HRID 1056490Notes

Reaction equation

HRID 1056490 reaction equation
Cl[S:2]([C:5]1[CH:6]=[CH:7][C:8]([F:14])=[C:9]([CH:13]=1)[C:10]([OH:12])=[O:11])(=[O:4])=[O:3].[CH:15]1([NH2:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:15]1([NH:21][S:2]([C:5]2[CH:6]=[CH:7][C:8]([F:14])=[C:9]([CH:13]=2)[C:10]([OH:12])=[O:11])(=[O:4])=[O:3])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 6089842-Fluoro-5-chlorosulfonylbenzoic acid

Product 1

HCID 20505863HCID 20505863, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Chlorosulfonyl-2-fluoro-benzoic acid (A, 0.508 g, 0.0021 mol), Cyclohexylamine (G, 0.211 g, 0.00212 mol) and DIEA (1.1 mL, 0.00636 mol) in CH2Cl2 were stirred at room temperature overnight. The solvent was evaporated and the crude product was purified by silica gel chromatography (MeOH containing 10% AcOH)/CH2Cl2) to give 5-cyclohexylsulfamoyl-2-fluoro-benzoic acid (H, 0.6 g, 95%). After drying overnight under vacuum, H (0.22 g, 0.737 mmol) in SOC12 (5 mL) was heated at 80° C. for 2 hours after which the SOCl2 was evaporated and the residue was dried overnight. The residue was then dissolved in tetrahydrofuran (5 mL), 3,4-difluoro-phenylamine (D, 95 mg, 0.737 mmol) was added followed by DIEA (0.8 mL). The mixture was heated to 70° C. overnight. The solvent was evaporated, followed by ethyl acetate extraction. After purification by silica gel chromatography (ethyl acetate/hexane), 0.192 g (63%) of 5-cyclohexylsulfamoyl-N-(3,4-difluoro-phenyl)-2-fluoro-benzamide (DVR-45) was obtained.

Workup

  1. customThe solvent was evaporated
  2. customthe crude product was purified by silica gel chromatography (MeOH containing 10% AcOH)/CH2Cl2)

Sources & evidence

ORD record
ord-f58a19e00d29405bad48709fc9640e9c
Source dataset
uspto-grants-2016_07
Patent number
US09399619B2

Reaction notes

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