1-Hydroxybenzotriazole → 5-{2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylcarbamoyl}-1H-pyrazole-3-carboxylic acid

HRID 872431Notes

Reaction equation

HRID 872431 reaction equation
O.[NH:2]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]([C:10]([OH:12])=O)=[N:3]1.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.Cl.[Cl:36][C:37]1[CH:38]=[C:39]([C:44]2[O:48][C:47]([CH2:49][CH2:50][NH2:51])=[CH:46][CH:45]=2)[CH:40]=[CH:41][C:42]=1[Cl:43]>CN(C=O)C.C(Cl)Cl.CCN(C(C)C)C(C)C.O>[Cl:36][C:37]1[CH:38]=[C:39]([C:44]2[O:48][C:47]([CH2:49][CH2:50][NH:51][C:10]([C:4]3[NH:3][N:2]=[C:6]([C:7]([OH:9])=[O:8])[CH:5]=3)=[O:12])=[CH:46][CH:45]=2)[CH:40]=[CH:41][C:42]=1[Cl:43]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27237231H-Pyrazole-3,5-dicarboxylic acid monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671683442-(5-(3,4-Dichlorophenyl)furan-2-yl)ethanamine hydrochloride

Product 1

HCID 1785244995-{2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylcarbamoyl}-1H-pyrazole-3-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 81531DiisopropylethylamineSolvent3×

Procedure

3,5-Pyrazoledicarboxylic acid monohydrate (8.02 g, 46.1 mmol) was dissolved in the mixture of dry DMF (35 ml), dry DCM (35 ml) and DIPEA (7.9 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 3.37 g, 17.6 mmol), HOBt (2.28 g, 16.9 mmol), and DIPEA (3 ml, 2.23 g, 17.3 mmol) were added at RT. The solution was mixed for 10 min. Then, 2-[5-(3,4-dichlorophenyl)-furan-2-yl]ethylamine hydrochloride (3.46 g, 11.8 mmol) dissolved in the mixture of dry DCM (35 ml) and DIPEA (2.0 ml, 1.48 g, 11.5 mmol) was dropped to the solution at RT. After stirring overnight water was added. The product was extracted into ethyl acetate. The organic phase was washed with water, dried and evaporated. The crude product was purified by flash chromatography using DCM as an eluent. The product was triturated in hot methanol. 1H NMR (400 MHz, DMSO-d6): 2.95 (2H, t), 3.56 (2H, m), 6.33 (1H, d), 7.01 (1H, d), about 7.03 (1H, broad s), 7.61 (1H, distorted dd), 7.63 (1H, distorted d), 7.83 (1H, d), about 8.45 (1H, broad s), about 14.05 (1H, broad s).

Workup

  1. additionThe solution was mixed for 10 min
  2. additionwas dropped to the solution at RT
  3. additionwas added
  4. extractionThe product was extracted into ethyl acetate
  5. washThe organic phase was washed with water
  6. customdried
  7. customevaporated
  8. customThe crude product was purified by flash chromatography
  9. customThe product was triturated in hot methanol

Sources & evidence

ORD record
ord-98bca7bdf9f644b2a38386d818e5271b
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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