1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl ester

HRID 251363Notes

Reaction equation

HRID 251363 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2].CCN=C=N[CH2:28][CH2:29][CH2:30][N:31](C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C1(N)CC1>CN(C=O)C.CCOC(C)=O.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18](=[O:20])[NH:31][CH:30]3[CH2:28][CH2:29]3)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 670242365-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

Product 1

HCID 112215565-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl esterYield 17.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (150 mg, 0.49 mmol, 1.0 eq), EDCI (190 mg, 0.98 mmol, 2.0 eq), HOBt (134 mg, 0.98 mmol, 2.0 eq), and diisopropylethyl amine (362 μL, 0.98 mmol, 2.0 eq) in DMF (5 mL) which had been stirred at RT for 15 min was added cyclopropylamine (68 μL, 0.98 mmol, 2.0 eq). After stirring overnight, the solution was diluted with EtOAc and water and the organic layer was washed with water (2×) and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography on silica gel (gradient elution, 3/2 EtOAc/hexanes then 100% EtOAc) to provide the product as a white solid (29 mg, 17%). HPLC (4 minute 10-95 gradient) tR 1.97 min; MS m/z 343 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.1 Hz, 1 H), 7.76 (s, 1 H), 7.50 (d, J=8.0 Hz, 1 H), 4.29 (q, J=7.0 Hz, 2 H), 2.84 (m, 1 H), 2.34 (s, 3 H), 2.18 (s, 3 H), 1.36 (t, J=7.0 Hz, 3 H), 0.79 (d, J=5.5 Hz, 2 H), 0.62 (s, 2 H) ppm; 13C NMR (CD3OD), δ 168.1, 164.4, 151.3, 149.8, 140.1, 135.2, 132.6, 130.7, 127.9, 126.3, 92.0, 58.6, 22.1, 15.7, 12.9, 12.6, 4.6 ppm.

Workup

  1. washthe organic layer was washed with water (2×) and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude residue was purified by flash chromatography on silica gel (
  5. washgradient elution, 3/2 EtOAc/hexanes

Sources & evidence

ORD record
ord-2ec46dc7760047bba21845c525865928
Source dataset
uspto-grants-2011_01
Patent number
US07863314B2

Reaction notes

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