Dimethylamine → HCID 22050379, compound

HRID 1867129Notes

Reaction equation

HRID 1867129 reaction equation
[CH3:1][N:2]([CH3:11])[C:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:12][C:13]1[C:14](=[O:40])[N:15]([CH2:30]C2C=CC(C(O)=O)=CC=2)[C:16]([CH3:29])=[CH:17][C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CNC.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.O>[Cl:12][C:13]1[C:14](=[O:40])[N:15]([CH2:30][C:7]2[CH:6]=[CH:5][C:4]([C:3]([N:2]([CH3:11])[CH3:1])=[O:10])=[CH:9][CH:8]=2)[C:16]([CH3:29])=[CH:17][C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28]

Participants

9

Reactant 6

HCID 674DimethylamineHCID 79724-MethylmorpholineHCID 11916N,N-DimethylbenzamideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220509654-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}benzoic acid

Product 1

HCID 22050379HCID 22050379, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Preparation of 4-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}}-N,N-dimethylbenzamide. 4-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}benzoic acid (2.00 g, 4.76 mmol) was suspended in N,N-dimethylformamide (20 mL). 1-Hydroxybenzotriazole (0.773 g, 5.72 mmol) was added followed by 4-methylmorpholine (1.57 mL, 14.28 mmol), dimethylamine (7.14 mL, 2.0 M in tetrahydrofuran, 14.28 mmol) and then 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.28 g, 6.66 mmol). The resulting mixture was stirred at room temperature for 3 hours at which time the reaction was diluted with H2O (75 mL). The reaction mixture was then extracted with ethyl acetate. The combined organic extracts were washed with saturated NaHCO3, brine, dried over Na2SO4, filtered and concentrated. The resulting solid was washed with ethyl acetate to provide the title compound as a white solid (1.67 g, 78%). 1H NMR (400 MHz, CDCl3) δ 7.53 (app q, J=7.8 Hz, H), 7.33 (d, J=8.3 Hz, 2H), 7.16 (d, J=8.3 Hz, 2H), 6.95-6.90 (m, 1H), 6.84 (app dt, J=2.5, 9.4 Hz, 1H), 6.02 (s, 1H), 5.35 (s, 2H), 5.19 (s, 2H), 2.97-2.93 (br m, 6H), 2.26 (s, 3H). ES-HRMS m/z 447.1246 (M+H calcd for C23H22ClF2N2O3 requires 447.1282).

Workup

  1. extractionThe reaction mixture was then extracted with ethyl acetate
  2. washThe combined organic extracts were washed with saturated NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washThe resulting solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-17c021efb5d34b68921daa48131cce68
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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