Isobutyraldehyde → 3,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxy-N-(3-((isobutyl amino)methyl)benzyl)benzene sulfonamide

HRID 1889680Notes

Reaction equation

HRID 1889680 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:34]=[CH:35][CH:36]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[S:8]([C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:12]=1[OH:19])(=[O:10])=[O:9].[CH:37](=O)[CH:38]([CH3:40])[CH3:39].[BH4-].[Na+]>CO>[Cl:18][C:13]1[C:12]([OH:19])=[C:11]([S:8]([N:7]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)[CH2:6][C:5]2[CH:34]=[CH:35][CH:36]=[C:3]([CH2:2][NH:1][CH2:37][CH:38]([CH3:40])[CH3:39])[CH:4]=2)(=[O:10])=[O:9])[CH:16]=[C:15]([Cl:17])[CH:14]=1

Participants

5

Reactant 3

HCID 6561IsobutyraldehydeHCID 4311764Sodium borohydrideHCID 58531533N-(3-(Aminomethyl)benzyl)-3,5-dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxybenzenesulfonamide

Product 1

HCID 585313773,5-Dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxy-N-(3-((isobutyl amino)methyl)benzyl)benzene sulfonamideYield 92.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-(Aminomethyl)benzyl)-3,5-dichloro-N-((4′-fluorobiphenyl-4-yl)methyl)-2-hydroxybenzenesulfonamide (1.0 g, 1.8 mmol, 1.0 eq) was dissolved in dry methanol. The solution was stirred for 10 minutes and treated with isobutyraldehyde (145 mg, 2 mmol, 1.1 eq). The resulting mixture was stirred for 10 minutes at ambient temperature, refluxed for 3 h, cooled to 0° C. and treated with NaBH4 (210 mg, 5.5 mmol, 3 eq). The mixture was stirred for 30 min at 0° C., quenched by the addition of 10% aq. NaHCO3 solution and stirred for 1 h at ambient temperature. The solvent was evaporated under reduced pressure and ethyl acetate was added. The organic layer was washed with water and dried with anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel (240-280) column chromatography using 10-20% ethyl acetate/hexane as the eluent to afford the desired product (1 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ 0.92-0.94 (s, 6H), 2.0 (t, 1H), 2.67-2.69 (d, 2H), 4.0 (s, 2H), 4.43-4.44 (s, 4H), 7.15-7.16 (d, 2H), 7.22-7.30 (m, 6H), 7.35 (s, 1H), 7.48-7.53 (d, 2H), 7.63-7.64 (d, 1H), 7.65-7.67 (t, 2H). MS (ESI): 602.2 (M+H)+.

Workup

  1. stirringThe resulting mixture was stirred for 10 minutes at ambient temperature
  2. temperaturerefluxed for 3 h
  3. stirringThe mixture was stirred for 30 min at 0° C.
  4. customquenched by the addition of 10% aq. NaHCO3 solution
  5. stirringstirred for 1 h at ambient temperature
  6. customThe solvent was evaporated under reduced pressure and ethyl acetate
  7. additionwas added
  8. washThe organic layer was washed with water
  9. dry with materialdried with anhydrous Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel (240-280) column chromatography

Sources & evidence

ORD record
ord-a463bc63de5e4d90b8262c102b70b92b
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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