Water → 6-Chloro-N-(3-chloro-5-((3,5-dichloro-2-hydroxy-N-isobutylphenylsulfonamido)methyl)benzyl)-N-isobutylnicotinamide

HRID 1889643Notes

Reaction equation

HRID 1889643 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1.O.[Cl:34][C:35]1[C:36]([OH:64])=[C:37]([S:42]([N:45]([CH2:50][C:51]2[CH:56]=[C:55]([CH2:57][NH:58][CH2:59][CH:60]([CH3:62])[CH3:61])[CH:54]=[C:53]([Cl:63])[CH:52]=2)[CH2:46][CH:47]([CH3:49])[CH3:48])(=[O:44])=[O:43])[CH:38]=[C:39]([Cl:41])[CH:40]=1>CN(C=O)C.C([O-])(O)=O.[Na+].C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:58]([CH2:57][C:55]2[CH:56]=[C:51]([CH2:50][N:45]([CH2:46][CH:47]([CH3:49])[CH3:48])[S:42]([C:37]3[CH:38]=[C:39]([Cl:41])[CH:40]=[C:35]([Cl:34])[C:36]=3[OH:64])(=[O:44])=[O:43])[CH:52]=[C:53]([Cl:63])[CH:54]=2)[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:8])=[CH:4][N:3]=1

Participants

9

Reactant 5

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 792226-Chloronicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 585315243,5-Dichloro-N-(3-chloro-5-((isobutylamino)methyl)benzyl)-2-hydroxy-N-isobutylbenzenesulfonamide

Product 1

HCID 585313546-Chloro-N-(3-chloro-5-((3,5-dichloro-2-hydroxy-N-isobutylphenylsulfonamido)methyl)benzyl)-N-isobutylnicotinamideYield 47.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 6-chloronicotinic acid (34.1 mg, 0.22 mmol) in DMF (4 mL) were added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (60 mg, 032 mmol), HOBt.H2O (30 mg, 0.20 mmol) and 3,5-dichloro-N-(3-chloro-5-((isobutylamino)methyl)benzyl)-2-hydroxy-N-isobutylbenzenesulfonamide (100 mg, 0.20 mmol). The resulting reaction mixture was stirred at rt. for 18 h. The mixture was diluted with saturated NaHCO3 solution and ethyl acetate. The organic layer was concentrated. The residue was dissolved in 1 N NaOH solution and THF for 2 h. The mixture was concentrated and dissolved in MeOH, purified by preparative HPLC. Fractions containing the desired product were combined, concentrated, and lyophilized to give the desired product as white solid (62 mg, 40%). 1H NMR (CD3OD): δ 8.50-8.35 (m 1H), 8.0-7.8 (m, 1H), 7.70-7.49 (m, 3H), 7.34 (m, 1H), 7.16 (m, 1H), 7.10 (m, 1H), 4.72-4.45 (m, 4H), 3.30-3.03 (m, 4H), 2.1-1.6 (m, 2H), 0.96-0.71 (m, 12H); MS (ESI): (M−H)−=646.0.

Workup

  1. customThe resulting reaction mixture
  2. concentrationThe organic layer was concentrated
  3. dissolutionThe residue was dissolved in 1 N NaOH solution
  4. waitTHF for 2 h
  5. concentrationThe mixture was concentrated
  6. dissolutiondissolved in MeOH
  7. custompurified by preparative HPLC
  8. additionFractions containing the desired product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e0d275eaa3c44dc6bd3ad4c5787b40e9
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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