1-Hydroxybenzotriazole → 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093640Notes

Reaction equation

HRID 1093640 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([CH3:13])[N:11]=[C:10]([C:14]([OH:16])=O)[CH:9]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:49][CH2:50][C:51]([N:53]1[CH2:58][CH2:57][CH:56]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[Cl:66])[CH2:55][CH2:54]1)=[O:52]>CN(C=O)C.O>[Cl:66][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=1[NH:59][CH:56]1[CH2:55][CH2:54][N:53]([C:51](=[O:52])[CH2:50][NH:49][C:14]([C:10]2[CH:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:12]([CH3:13])[N:11]=2)=[O:16])[CH2:58][CH2:57]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915702-Amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone hydrochlorideHCID 1361706645-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 1359151865-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid (0.13 g, 0.0006 mol) in DMF (2 mL) was added DIPEA (0.308 g, 0.00234 mol), HOBt (0.101 g, 0.00075 mol) and EDCI.HCl (0.143 g, 0.00075 mol) at ambient temperature. After 5 minutes 2-amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone hydrochloride (0.181 g, 0.00060 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 recrystallized from ethyl acetate to afford 0.113 g (41%) of 5-(2-hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 468.18 (M+1)+, 96.98%. 1H NMR (DMSO-d6): δ 10.2 (s, 1H), 8.7 (t, 1H), 7.7 (d, 1H), 7.4 (s, 1H), 7.1 (m, 3H), 6.8 (m, 3H), 6.6 (m, 1H), 4.9 (m, 1H), 4.3 (d, 1H), 4.1 (m, 4H), 3.9 (m, 1H), 3.6 (m, 1H), 3.1 (m, 1H), 2.7 (m, 1H), 1.9 (m, 2H), 1.4 (m, 2H).

Workup

  1. customThe resulting precipitate was isolated by filtration
  2. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-c5ba601f57c148a0894a26637a69b749
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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