1-Hydroxybenzotriazole → [(6-Phenylamino-pyridine-3-carbonyl)-amino]-acetic acid ethyl ester

HRID 1093655Notes

Reaction equation

HRID 1093655 reaction equation
[C:1]1([NH:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH2:49]([O:51][C:52](=[O:55])[CH2:53][NH2:54])[CH3:50]>CN(C=O)C.O>[CH2:49]([O:51][C:52](=[O:55])[CH2:53][NH:54][C:12]([C:11]1[CH:10]=[N:9][C:8]([NH:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:16][CH:15]=1)=[O:14])[CH3:50]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2723640Glycine ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27718126-(Phenylamino)nicotinic acid

Product 1

HCID 66591629[(6-Phenylamino-pyridine-3-carbonyl)-amino]-acetic acid ethyl esterYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-phenylamino-nicotinic acid (0.1 g, 0.00047 mol) in DMF (2 mL), was added DIPEA (0.181 g, 0.001401 mol), HOBt (0.0756 g, 0.00056 mol) and EDCI.HCl (0.107 g, 0.00056 mol) at ambient temperature. After 2 minutes glycine ethyl ester hydrochloride (0.0782 g, 0.00056 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water. The resulting precipitate was isolated by filtration and purified by column chromatography using silica gel 60-120 mesh (60% ethyl acetate in hexane) to afford 0.135 g (97%) of [(6-phenylamino-pyridine-3-carbonyl)-amino]-acetic acid ethyl ester. LCMS: 299.13 (M+1)+, 99%. To a stirred solution of [(6-phenylamino-pyridine-3-carbonyl)-amino]-acetic acid ethyl ester (0.135 g, 0.00045 mol) in a mixture of THF (5 mL), methanol (7 mL) and H2O (2 mL) was added LiOH.H2O (0.0568 g, 0.00135 mol) at ambient temperature and the resulting mixture was stirred for 2 hours. Volatiles were then evaporated and the resulting residue was diluted with water, acidified with 10% aqueous HCl solution. The resulting precipitate was isolated by filtration and dried to afford 0.078 g (64%) of [(6-phenylamino-pyridine-3-carbonyl)-amino]-acetic acid.

Workup

  1. customThe resulting precipitate was isolated by filtration
  2. custompurified by column chromatography

Sources & evidence

ORD record
ord-7737b05eb79949e3873ea217765d4ea9
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…