Methylamine → 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-N,N'-dimethylterephthalamide

HRID 1832114Notes

Reaction equation

HRID 1832114 reaction equation
[Br:1][C:2]1[C:3](=[O:32])[N:4]([C:19]2[CH:27]=[C:26]([C:28]([NH:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:20]=2[C:21]([OH:23])=O)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].Cl.[CH3:34][N:35](C)CCCC(N=C=N)C.ON1C2C=CC=CC=2N=N1.CN>CN(C=O)C.C(OCC)(=O)C.C(#N)C.O>[Br:1][C:2]1[C:3](=[O:32])[N:4]([C:19]2[CH:27]=[C:26]([C:28]([NH:30][CH3:31])=[O:29])[CH:25]=[CH:24][C:20]=2[C:21]([NH:35][CH3:34])=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 219829211-(3-Dimethylaminopropyl)ethylcarbodiimide hydrochlorideHCID 220508892-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-[(methylamino)carbonyl] benzoic Acid

Product 1

HCID 220503552-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-N,N'-dimethylterephthalamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a room temperature solution of 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-[(methylamino)carbonyl]benzoic acid (500 mg, 0.986 mmol) in DMF (5.0 mL) was added 1-(3-dimethylaminopropyl)-ethylcarbodiimide hydrochloride (EDC-HCl, 350.0 mg, 1.83 mmol) and 1-hydroxy-benzotriazole (HOBT, 100.0 mg, 0.74 mmol) sequentially. To this resulting suspension was then added a solution of methylamine (2.0 M THF, 1.0 mL, 2.0 mmol). The reaction was stirred for 16.0 hours, at which time the reaction was diluted with ethyl acetate (600 mL). The mixture was washed with (3×200 mL) of water and the organic extract was separated, Na2SO4 dried, and concentrated in vacuo to a volume of approximately 60 mL. At this time a solid precipitate formed and was collected to furnish (289 mg, 56%). 1H NMR (300 MHz, d4-MeOH) δ 8.06 (br d, J=8.0 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.73 (s, 1H), 7.70 (app q, J=7.4 Hz, 1H), 7.09 (app t, J=8.0 Hz, 2H), 6.65 (s, 1H), 5.39 (s, 2H), 2.96 (s, 3H), 2.79 (s, 3H), 2.13 (s, 3H); LC/MS C-18 column, tr=2.13 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 520 (M+H). ES-HRMS m/z 520.0700 (M+H calcd for C23H21BrF2N3O4 requires 520.0678).

Workup

  1. washThe mixture was washed with (3×200 mL) of water
  2. extractionthe organic extract
  3. customwas separated
  4. dry with materialNa2SO4 dried
  5. concentrationconcentrated in vacuo to a volume of approximately 60 mL
  6. customAt this time a solid precipitate formed
  7. customwas collected
  8. customto furnish (289 mg, 56%)

Sources & evidence

ORD record
ord-c7997ab6355a4c23a97897cfff5ab1ea
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

Loading…