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

HRID 872442Notes

Reaction equation

HRID 872442 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([C:8]([OH:10])=O)=[N:3]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[Cl:43][C:44]1[CH:45]=[C:46]([C:51]2[O:55][C:54]([CH2:56][CH2:57][NH2:58])=[CH:53][CH:52]=2)[CH:47]=[CH:48][C:49]=1[Cl:50]>CN(C=O)C.O>[Cl:43][C:44]1[CH:45]=[C:46]([C:51]2[O:55][C:54]([CH2:56][CH2:57][NH:58][C:8]([C:4]3[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=3)=[O:10])=[CH:53][CH:52]=2)[CH:47]=[CH:48][C:49]=1[Cl:50]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 5877571,5-dimethyl-1H-pyrazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671683442-(5-(3,4-Dichlorophenyl)furan-2-yl)ethanamine hydrochloride

Product 1

HCID 706569031,5-Dimethyl-1H-pyrazole-3-carboxylic acid {2-[5-(3,4-dichlorophenyl)furan-2-yl]ethyl}amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1,5-Dimethyl-1H-pyrazole-3-carboxylic acid (100 mg, 0.71 mmol) was dissolved in dry DMF (2 ml). EDCl (205 mg, 1.1 mmol), HOBt (145 mg, 1.1 mmol) and DIPEA (0.19 ml, 141 mg, 1.1 mmol) were added at RT. The solution was stirred for 30 min. Then, 2-[5-(3,4-dichlorophenyl)furan-2-yl]ethylamine hydrochloride (313 mg, 1.1 mmol) dissolved in the mixture of dry DMF (4 ml) and DIPEA (0.19 ml, 141 mg, 1.1 mmol) was added 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 CH2Cl2-MeOH as a gradient eluent (100:0-95:5). Another purification was done also by flash chromatography using CH2Cl2-MeOH as a gradient eluent (100:0-99.7:0.3). The product was triturated in heptane-CH2Cl2 at RT. 1H NMR (400 MHz, DMSO-d6): 2.26 (3H, s), 2.92 (2H, t), 3.52 (2H, m), 3.76 (3H, s), 6.31 (1H, d), 6.38 (1H, s), 7.01 (1H, d), 7.60 (1H, distorted dd), 7.64 (1H, distorted d), 7.83 (1H, d), 8.09 (1H, t).

Workup

  1. additionwas added to the solution at RT
  2. additionwas added
  3. extractionThe product was extracted into ethyl acetate
  4. washThe organic phase was washed with water
  5. customdried
  6. customevaporated
  7. customThe crude product was purified by flash chromatography
  8. customAnother purification
  9. customThe product was triturated in heptane-CH2Cl2 at RT

Sources & evidence

ORD record
ord-5d3145c290084171a7a00f6e8c297fa5
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

Loading…