2,6-Dichlorobenzoyl chloride → N-(3-fluoropyridin-4-yl)-2,6-dichlorobenzamide

HRID 449930Notes

Reaction equation

HRID 449930 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH2:8].CCN(C(C)C)C(C)C.[Cl:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:20]=1[C:21](Cl)=[O:22]>ClCCl.CC#N>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][C:21](=[O:22])[C:20]1[C:19]([Cl:18])=[CH:27][CH:26]=[CH:25][C:24]=1[Cl:28]

Participants

6

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 8171224-Amino-3-fluoropyridine

Product 1

HCID 59618080N-(3-fluoropyridin-4-yl)-2,6-dichlorobenzamideYield 47.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a cooled (0° C.) mixture of 3-fluoropyridin-4-amine (1.0 g, 8.9 mmol) and DIPEA (2.7 mL, 18 mmol) in dichloromethane (20 mL) and MeCN (10 mL) was added a solution of 2,6-dichlorobenzoyl chloride (2.1 g, 9.8 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was partitioned between EtOAc (30 mL) and sat. NaHCO3 (30 mL). The aqueous layer was extracted with EtOAc (2×15 mL) and then the combined organic extracts were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc) to afford N-(3-fluoropyridin-4-yl)-2,6-dichlorobenzamide (1.2 g, yield: 47%). 1H NMR (400 MHz, DMSO) δ 11.21 (s, 1H), 8.59 (d, J=2.8, 1H), 8.41 (d, J=5.4, 1H), 8.21 (dd, J=6.7, 5.4, 1H), 7.77-7.33 (m, 3H). LCMS (ESI) m/z: 285.2 [M+H+]

Workup

  1. temperatureTo a cooled
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between EtOAc (30 mL) and sat. NaHCO3 (30 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
  5. concentrationthe combined organic extracts were concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-ac4191c165004976b2b536ab8378f3fd
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

Loading…