Hydrochloric Acid → Methyl 5-[(4,5-dichloro-2-fluoro-benzoyl)amino]pyridine-2-carboxylate

HRID 515072Notes

Reaction equation

HRID 515072 reaction equation
[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6](Cl)=[O:7])=[C:4]([F:12])[CH:3]=1.[NH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([O:22][CH3:23])=[O:21])=[N:18][CH:19]=1.N1C=CC=CC=1.Cl>ClCCl.CCCCCC>[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]([O:22][CH3:23])=[O:21])=[N:18][CH:19]=2)=[O:7])=[C:4]([F:12])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 12457877Methyl 5-aminopyridine-2-carboxylateHCID 196123744,5-Dichloro-2-fluorobenzoylchloride

Product 1

HCID 90314668Methyl 5-[(4,5-dichloro-2-fluoro-benzoyl)amino]pyridine-2-carboxylateYield 81.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8058HexaneSolvent

Procedure

A solution of 4,5-dichloro-2-fluoro-benzoyl chloride (4.35 g, 19.13 mmol) in dichloromethane (40 mL) was added drop-wise to a mixture of methyl 5-aminopyridine-2-carboxylate (2.91 g, 19.13 mmol), pyridine (4.64 mL, 57.39 mmol) and dichloromethane (60 mL) at 0° C. The reaction was stirred and allowed to warm up to room temperature over 2 hours. The mixture was poured into 1N HCl (50 mL) and dichloromethane (50 mL). The two layers were separated. The aqueous layer was extracted with dichloromethane (3×200 mL). The combined organic layer was washed with water (1×150 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was slurried in hexanes to remove impurities. The solid was isolated by filtration using hexane to yield methyl 5-[(4,5-dichloro-2-fluoro-benzoyl)amino]pyridine-2-carboxylate (5.33 g, 81%) as a cream color solid. 1H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.94 (d, J=2.5 Hz, 1H), 8.36 (dd, J=8.6, 2.5 Hz, 1H), 8.12 (d, J=8.6 Hz, 1H), 8.08 (d, J=6.6 Hz, 1H), 7.95 (d, J=9.6 Hz, 1H), 3.87 (s, 3H) ppm. ESI-MS m/z calc. 342.00, found 343.1 (M+1)+; Retention time: 1.72 minutes (3 minutes run).

Workup

  1. customThe two layers were separated
  2. extractionThe aqueous layer was extracted with dichloromethane (3×200 mL)
  3. washThe combined organic layer was washed with water (1×150 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto remove impurities
  8. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-c82537d4802043fd92370b2b88b07f56
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

Loading…