1-Hydroxybenzotriazole → N-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)ethyl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazole-3-carboxamide

HRID 872480Notes

Reaction equation

HRID 872480 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[NH:5][C:4]([C:13]([OH:15])=O)=[CH:3]1.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[NH2:38][CH2:39][CH2:40][N:41]1[CH:45]=[CH:44][C:43]([C:46]2[CH:53]=[CH:52][C:49]([C:50]#[N:51])=[C:48]([Cl:54])[CH:47]=2)=[N:42]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:54][C:48]1[CH:47]=[C:46]([C:43]2[CH:44]=[CH:45][N:41]([CH2:40][CH2:39][NH:38][C:13]([C:4]3[NH:5][N:6]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)[C:2](=[O:1])[CH:3]=3)=[O:15])[N:42]=2)[CH:53]=[CH:52][C:49]=1[C:50]#[N:51]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 91673915-oxo-1-phenyl-2,5-dihydro-1H-pyrazole-3-carboxylic acidHCID 671701664-(1-(2-Aminoethyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 70656969N-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)ethyl)-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazole-3-carboxamideYield 17.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

5-Oxo-1-phenyl-2,5-dihydro-1H-pyrazole-3-carboxylic acid (0.05 g; 0.24 mmol), HOBt (0.049 g; 0.37 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.07 g; 0.37 mmol) were added to 2.5 ml of DCM. To this a mixture of 4-(1-(2-aminoethyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (0.06 g; 0.24 mmol) and DIPEA (0.064 ml; 0.37 mmol) was added dropwise and the mixture was stirred overnight after which 10 ml of DCM was added. The mixture was washed with 3×5 ml of water and the combined water phases were extracted with 2×5 ml of DCM. The combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The product was purified with flash chromatography using DCM/MeOH as gradient eluent. The combined fractions gave 18 mg of the product. 1H-NMR (400 MHz; d6-DMSO): δ 1.23 (s, 1H), 3.65-3.70 (m, 2H), 4.37 (t, 2H), 5.83 (s, 1H), 6.97 (d, 1H), 7.31-7.35 (t, 1H), 7.45-7.49 (t, 2H), 7.76 (d, 2H), 7.85-7.89 (m, 2H), 7.94-7.96 (m, 1H), 8.09 (d, 1H), 8.28 (m, 1H).

Workup

  1. additionwas added dropwise
  2. additionwas added
  3. washThe mixture was washed with 3×5 ml of water
  4. extractionthe combined water phases were extracted with 2×5 ml of DCM
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe product was purified with flash chromatography

Sources & evidence

ORD record
ord-97f8f997c455440bbad26e1c88c1cfd7
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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