4-Methylmorpholine → HCID 22050145, compound

HRID 1866946Notes

Reaction equation

HRID 1866946 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[CH2:6][N:7]1[C:12]([CH3:13])=[CH:11][C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2[F:23])=[C:9]([Br:24])[C:8]1=[O:25].ON1C2C=C[CH:37]=[CH:38][C:33]=2N=N1.Cl.CN(C)CCCN=C=NCC.CN1C[CH2:56][O:55]CC1.CN(C)C(=[O:62])C>O>[Br:24][C:9]1[C:8](=[O:25])[N:7]([CH2:6][C:5]2[CH:4]=[C:3]([CH:28]=[CH:27][CH:26]=2)[CH2:2][NH:1][C:56](=[O:55])[C:38]([OH:62])([CH3:37])[CH3:33])[C:12]([CH3:13])=[CH:11][C:10]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 31374DimethylacetamideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11155124HCID 11155124, compound

Product 1

HCID 22050145HCID 22050145, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-[3-(aminomethyl)benzyl]-3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (EXAMPLE 161) (0.300 g, 0.668 mmol), 1-hydroxyisobutyric acid (0.215 g, 2.064 mmol), 1-hydroxybenzotriazole (0.112 g, 0.826 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.185 g, 0.963 mmol) were dissolved in N,N-dimethylacetamide (3 mL). N-methylmorpholine (0.209 g, 2.064 mmol) was added, and the reaction stirred for 1 hour at room temperature. The reaction was diluted with H2O (50 mL) and the aqueous layer extracted with ethyl acetate (3×25 mL). The combined organics were then washed with 1N HCl (25 mL), saturated Na2CO3 (25 mL), brine (25 mL), dried over Na2SO4, and concentrated to yield an off-white solid (0.235 g, 64%). 1H NMR (400 MHz, DMF-d6) δ 8.25 (br s, 1H), 7.81 (app q, J=7.92 Hz, 1H), 7.40-7.21 (m, 5H), 7.09 (d, J=6.84 Hz, 1H), 6.67 (s, 1H), 5.46 (s, 2H), 5.42 (s, 2H), 4.42 (d, J=6.24 Hz, 2H), 2.44 (s, 3H), 1.38 (s, 6H). ES-HRMS m/z 535.1024 (M+H C25H25BrF2N2O4 requires 535.1039).

Workup

  1. extractionthe aqueous layer extracted with ethyl acetate (3×25 mL)
  2. washThe combined organics were then washed with 1N HCl (25 mL), saturated Na2CO3 (25 mL), brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ce163f1b42534b51aa9d6fd69472363b
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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