Triethylamine → 5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-(2-hydroxy-ethoxy)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 2041059Notes

Reaction equation

HRID 2041059 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]([C:11]#[N:12])=[C:6]1[O:10][CH2:9][CH2:8][O:7]1)[CH3:2].FC(F)(F)C(O)=O.[CH:21]1([NH:24][C:25](=[O:35])[C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH:33][NH2:34])[CH:27]=2)[CH2:23][CH2:22]1.C(N(CC)CC)C>C(O)C>[CH2:1]([O:3][C:4]([C:5]1[C:6]([O:7][CH2:8][CH2:9][OH:10])=[N:34][N:33]([C:28]2[CH:27]=[C:26]([C:25](=[O:35])[NH:24][CH:21]3[CH2:23][CH2:22]3)[CH:31]=[CH:30][C:29]=2[CH3:32])[C:11]=1[NH2:12])=[O:13])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2766691Ethyl cyano(1,3-dioxolan-2-ylidene)acetateHCID 67024207N-cyclopropyl-3-hydrazinyl-4-methylbenzamide 2,2,2-trifluoroacetate

Product 1

HCID 248607185-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-(2-hydroxy-ethoxy)-1H-pyrazole-4-carboxylic acid ethyl esterYield 62.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1H), 7.78 (s, 1H), 7.49 (d, J=7.8 Hz, 1H), 4.29 (dd, J=14.9, 6.9 Hz, 2H), 4.19 (d, J=4.3 Hz, 2H), 3.84 (d, J=4.4 Hz, 2H), 2.84 (m, 1H), 2.22 (s, 3H), 1.35 (t, J=7.3 Hz, 3H), 0.81 (d, J=5.3 Hz, 2H), 0.63 (s, 2H) ppm.

Workup

  1. concentrationthe mixture was concentrated
  2. customthe residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

Sources & evidence

ORD record
ord-67cdf9f8f053473ba4544c6ca7f04c31
Source dataset
uspto-grants-2013_11
Patent number
US08580838B2

Reaction notes

Loading…