1-Hydroxybenzotriazole hydrate → N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-(3-methylsulfanyl-phenoxy)-nicotinamide

HRID 844055

Reaction equation

HRID 844055 reaction equation
[CH3:1][S:2][C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[O:6][C:7]1[N:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=O.[NH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C>CN(C)C=O.O>[OH:30][C:27]([C:24]1[CH:25]=[CH:26][C:21]([CH2:20][NH:19][C:9](=[O:11])[C:8]2[CH:12]=[CH:13][CH:14]=[N:15][C:7]=2[O:6][C:5]2[CH:16]=[CH:17][CH:18]=[C:3]([S:2][CH3:1])[CH:4]=2)=[CH:22][CH:23]=1)([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 27960291-Hydroxybenzotriazole hydrateHCID 101542112-[4-(aminomethyl)phenyl]propan-2-olHCID 218771742-[3-(Methylsulfanyl)phenoxy]nicotinic acidHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 22612047N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-(3-methylsulfanyl-phenoxy)-nicotinamideYield 14.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution 2-(3-Methylsulfanyl-phenoxy)-nicotinic acid (2.5 grams, 9.58 mmole), 2-(4-Aminomethyl-phenyl)-propan-2-ol (1.896 grams, 11.50 mmole) and 1-hydroxybenzotriazole hydrate (1.55 grams, 11.50 mmole) in dry dimethylformamide (60 ml) was added 1-(3-dimethylamino)-propyl)-3-ethylcarbodiimide hydrochloride (2.39 grams, 12.45 mmole) and stirred over night. The mixture was diluted with 300 ml water and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over MgSO4, filtered and concentrated to give a yellow oil that was purified by chromatography on silica eluting with 3.5% methanol/methylene chloride to give a white solid. Recrystalization from ethyl acetate/hexane gave a solid (0.550 g). M.P. 107-109° C.; Anal. calcd. for C23H24N2O3S: C, 67.62; H, 5.92; N, 6.86. Found: C, 67.53, H, 5.76; N, 6.91.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organics were washed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a yellow oil that
  7. customwas purified by chromatography on silica eluting with 3.5% methanol/methylene chloride
  8. customto give a white solid
  9. customRecrystalization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-61cf55dc6c854cc692ace2654e29efb5
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Linked notes

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