1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 62490Notes

Reaction equation

HRID 62490 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=2)C(O)=O)[C:5]([Cl:18])=[CH:4][N:3]=1.C[N:20]([CH3:29])CCCN=C=NCC.[OH:30]N1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:49]([O-])(O)=[O:50].[Na+]>CN(C)C=O.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:11][C:10]=2[C:29]([NH:20][O:50][CH3:49])=[O:30])[C:5]([Cl:18])=[CH:4][N:3]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 57516897HCID 57516897, compound

Product 1

HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[(2,5-dichloro-4-pyridinyl)amino]benzoic acid (500 mg, 1.766 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) (339 mg, 1.766 mmol) and 1-hydroxybenzotriazole (HOBT) (270 mg, 1.766 mmol) in N,N-dimethylformamide (3532 μl) was stirred at room temperature for 30 min. To this solution O-methylhydroxylamine(aminoxy)methane (148 mg, 1.766 mmol) was then added and stirred for another 10 min. The reaction mixture was cooled using an ice water bath. Then diisopropylethylamine (617 μl, 3.53 mmol) was added. After the addition was finished, the reaction mixture was stirred at room temperature overnight. The reaction mixture was followed by HPLC and LCMS. The final crude material was worked up by addition of saturated aqueous NaHCO3 and CH2Cl2. Organic phase was washed with brine then dried over MgSO4. The solution was filtered and solvent was removed by evaporation. The oil like crude material was loaded on silica column and eluted with MeOH in CH2Cl2 with NH4OH 0.1% to give the target compound 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (320 mg, 1.025 mmol, 58.0% yield) as a yellow solid; MS; M(C13H11Cl2N3O2)=312.15, (M+H)+=312, 313.9; 1H NMR (400 MHz, CHLOROFORM-d) ppm 9.66 (br. s., 1 H) 9.60 (br. s., 1 H) 8.20 (s, 1 H) 7.49-7.61 (m, 3 H) 7.24 (s, 1 H) 7.09-7.16 (m, 1 H) 3.90 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. additionAfter the addition
  3. stirringthe reaction mixture was stirred at room temperature overnight
  4. washOrganic phase was washed with brine
  5. dry with materialthen dried over MgSO4
  6. filtrationThe solution was filtered
  7. customsolvent was removed by evaporation
  8. washeluted with MeOH in CH2Cl2 with NH4OH 0.1%

Sources & evidence

ORD record
ord-8d56df3b4a1f4948976b811b2cf4f659
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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