Dimethylformamide → 6-chloro-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide

HRID 547502Notes

Reaction equation

HRID 547502 reaction equation
Cl[C:2]1[N:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[O:5].[Cl-].[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[CH2:24][CH2:25][NH2:26].C([O-])([O-])=O.[K+].[K+].[CH3:36]N(C=O)C.C(O[CH2:45][CH3:46])(=O)C>>[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[CH2:24][CH2:25][NH:26][C:2]1[N:17]=[C:16](/[CH:36]=[CH:45]/[CH3:46])[CH:15]=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[O:5].[Cl:18][C:16]1[CH:15]=[CH:14][C:3]([C:4]([NH:6][CH2:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[O:5])=[C:2]([NH:26][CH2:25][CH2:24][C:23]2[CH:27]=[CH:28][CH:29]=[C:21]([F:20])[CH:22]=2)[N:17]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5339282-(3-Fluorophenyl)ethanamineHCID 86620471chloride 2,6-dichloro-N-(pyridin-3-ylmethyl)nicotinamide

Product 2

HCID 597382236-chloro-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamideYield 46%HCID 59738250(E)-2-(3-fluorophenethylamino)-6-(prop-1-enyl)-N-(pyridin-3-ylmethyl)nicotinamide

Conditions

Temperature
10 °C

Procedure

A mixture of chloride 2,6-dichloro-N-(pyridin-3-ylmethyl)nicotinamide (20.4 g, 72.3 mmol), 3-fluorophenethyl amine (11.1 g, 79.5 mmol), K2CO3 (20 g 145 mmol) and DMF (200 mL) was stirred at 10° C. for 10 hours. The mixture was diluted with ethyl acetate (2×300 mL) and washed with saturated ammonium chloride, sodium bicarbonate and brine. The organic layers were combined, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography to give the desired product 6-chloro-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide (12.6 g, 46%). LRMS (M+H+) m/z 385.1.

Workup

  1. washwashed with saturated ammonium chloride, sodium bicarbonate and brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d0824b253fd74616a1745802944252ad
Source dataset
uspto-grants-2011_05
Patent number
US07939548B2

Reaction notes

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