N,N-Dimethylsulfamide → 5-chloro-4-((7,7-dimethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-N-(N,N-dimethylsulfamoyl)-2-fluorobenzamide

HRID 1849593Notes

Reaction equation

HRID 1849593 reaction equation
[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:23]=[CH:22][C:21]3[CH2:20][CH2:19][C:18]([CH3:25])([CH3:24])[CH2:17][C:16]=3[CH:15]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:26][N:27]([CH3:32])[S:28](=[O:31])(=[O:30])[NH2:29].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:23]=[CH:22][C:21]3[CH2:20][CH2:19][C:18]([CH3:25])([CH3:24])[CH2:17][C:16]=3[CH:15]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:29][S:28](=[O:31])(=[O:30])[N:27]([CH3:32])[CH3:26])=[O:8]

Participants

6

Reactant 3

HCID 134472N,N-DimethylsulfamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867029305-Chloro-4-((7,7-dimethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-2-fluorobenzoic acid

Product 1

HCID 867029315-chloro-4-((7,7-dimethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-N-(N,N-dimethylsulfamoyl)-2-fluorobenzamideYield 22.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-chloro-4-((7,7-dimethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)-2-fluorobenzoic acid (50 mg, 0.14 mmol), dimethyl(sulfamoyl)amine (326 mg, 0.20 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (38 mg, 0.20 mmol) and 4-dimethylaminopyridine (38 mg, 0.20 mmol) in DCM (3 mL) was stirred at room temperature for 16 hrs. The reaction was quenched with water (5 mL), adjusted pH to 5 with HCl (1M) and extracted with DCM (30 mL×3). The combined organic layers were concentrated and purified by reverse phase combiflash (20%-50% MeCN in 0.1% formic acid) to give the desired product (14.6 mg, 19%) as a white solid. LCMS (ESI) Method A: RT=6.47 min, m/z 466.9 [M−H]+; 1H-NMR (500 MHz, MeOD-d4) δ 7.63 (d, J=5.5 Hz, 1H), 7.32 (d, J=11.0 Hz, 1H), 6.91 (d, J=8.5 Hz, 1H), 6.66-6.63 (m, 1H), 6.56 (d, J=2.0 Hz, 1H), 5.03 (s, 2H), 2.83 (s, 6H), 2.64 (t, J=13.0 Hz, 2H), 2.40 (s, 2H), 1.46 (t, J=13.5 Hz, 2H), 0.88 (s, 6H).

Workup

  1. customThe reaction was quenched with water (5 mL)
  2. extractionextracted with DCM (30 mL×3)
  3. concentrationThe combined organic layers were concentrated
  4. custompurified by reverse phase combiflash (20%-50% MeCN in 0.1% formic acid)

Sources & evidence

ORD record
ord-c48c8f6ca1a84c519bee8ea12403eb9a
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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