Diisopropylethylamine → 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 1472533

Reaction equation

HRID 1472533 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11](O)=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1.Cl.CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.Cl.[O:42]([NH2:44])[CH3:43].C(N(C(C)C)CC)(C)C>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([NH:44][O:42][CH3:43])=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 575168952-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A vessel was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]benzoic acid (1.0 g, 3.53 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (677 mg, 3.53 mmol) and hydroxybenzotriazole (HOBT) (541 mg, 3.53 mmol) in N,N-dimethylformamide (DMF, 7.0 mL) and was stirred at room temperature for 30 min. To this solution methoxylamine hydrochloride (0.3 g, 3.53 mmol) was added and reaction mixture was stirred for another 10 min. The reaction mixture was cooled to 0° C. by using an ice bath. To this reaction mixture diisopropylethylamine (1.2 mL, 7.06 mmol) was added and the mixture was stirred at room temperature overnight. After concentrating under vacuum, the residue was worked up by using a saturated aqueous solution of NaHCO3 and CH2Cl2. The organic phase was washed with brine then dried over MgSO4 and filtered. The CH2Cl2 was removed by rotary evaporation. The crude material was loaded on silica gel column and eluted by MeOH in CH2Cl2 with NH4OH 0.1%, which gave the desired product 2-[(2, 5-dichloro-4-pyridinyl) amino]-N-(methyloxy)benzamide (850 mg, 2.72 mmol, 77% yield) MS: M(C13H11C12N3O2)=312.15, (M+H)+=312, 314; 1H NMR (400 MHz, CHLOROFORM-d)δ ppm 9.57 (br. s., 1 H) 8.72 (s, 1 H) 8.22 (s, 1 H) 7.51 - 7.67 (m, 3H) 7.25 (s, 1 H) 7.07 - 7.21 (m, 1 H) 3.92 (s, 3 H).

Workup

  1. customreaction mixture
  2. stirringwas stirred for another 10 min
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. stirringthe mixture was stirred at room temperature overnight
  5. concentrationAfter concentrating under vacuum
  6. washThe organic phase was washed with brine
  7. dry with materialthen dried over MgSO4
  8. filtrationfiltered
  9. customThe CH2Cl2 was removed by rotary evaporation
  10. washeluted by MeOH in CH2Cl2 with NH4OH 0.1%, which

Sources & evidence

ORD record
ord-9fa9ed6b879c433b967a630acaba90ff
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Linked notes

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