Pyridoxal hydrochloride → 4'-[(3-Hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamide

HRID 2373304Notes

Reaction equation

HRID 2373304 reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[C:6]([CH:9]=O)[C:5]([CH2:11][OH:12])=[CH:4][N:3]=1.Cl.[C:14]([NH:18][S:19]([C:22]1[C:23]([C:28]2[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=2)=[CH:24][CH:25]=[CH:26][CH:27]=1)(=[O:21])=[O:20])([CH3:17])([CH3:16])[CH3:15].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.CO>[C:14]([NH:18][S:19]([C:22]1[C:23]([C:28]2[CH:33]=[CH:32][C:31]([NH:34][CH2:9][C:6]3[C:5]([CH2:11][OH:12])=[CH:4][N:3]=[C:2]([CH3:1])[C:7]=3[OH:8])=[CH:30][CH:29]=2)=[CH:24][CH:25]=[CH:26][CH:27]=1)(=[O:21])=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 6171Pyridoxal hydrochlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydrideHCID 10804475N-tert-butyl-4'-aminobiphenyl-2-sulfonamide

Product 1

HCID 598525304'-[(3-Hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamideYield 24.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a 250 mL three-necked round bottom flask fitted with a condenser and a Dean-Stark trap, a mixture of pyridoxal hydrochloride (330 mg, 1.62 mmol), 4′-amino-biphenyl-2-sulfonic acid tert-butylamide (494 mg, 1.62 mmol), p-toluenesulfonic acid monohydrate (68 mg, 0.36 mmol) in toluene (150 mL) was heated at 100° C. under nitrogen atmosphere for 3 hours. The solvent was then evaporated and the crude product was dissolved in dichloromethane (70 mL), cooled down to 0° C. and then sodium borohydride (163 mg, 4.32 mmol) and methyl alcohol (15 mL) were added. The reaction mixture was stirred at room temperature overnight, after which the solvent was removed. The residue was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated. The crude product was purified by column chromatography on silica gel using a mixture of dichloromethane:methyl alcohol (9:1) as eluant to give 4′-[(3hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamide (7) (178 mg, 24% overall yield for two steps) as a colorless solid.

Workup

  1. customIn a 250 mL three-necked round bottom flask fitted with a condenser
  2. customThe solvent was then evaporated
  3. dissolutionthe crude product was dissolved in dichloromethane (70 mL)
  4. temperaturecooled down to 0° C.
  5. customafter which the solvent was removed
  6. additionThe residue was diluted with saturated aqueous sodium bicarbonate
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by column chromatography on silica gel using
  12. additiona mixture of dichloromethane:methyl alcohol (9:1) as eluant

Sources & evidence

ORD record
ord-6d63d71665c3433aa455905b45d11600
Source dataset
uspto-grants-2008_12
Patent number
US07459468B2

Reaction notes

Loading…