Triethylamine → HCID 178423845, compound

HRID 1832121Notes

Reaction equation

HRID 1832121 reaction equation
[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:19]2[CH:20]=[C:21]([C:26](=O)[CH2:27][C:28]([O:30]CC)=[O:29])[CH:22]=[CH:23][C:24]=2[CH3:25])[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].C([N:37](CC)CC)C.Cl.NO.C([O-])(O)=O.[Na+]>CCO.C(Cl)Cl.[Cl-].[Na+].O>[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:19]2[CH:20]=[C:21]([C:26]3[CH:27]=[C:28]([OH:30])[O:29][N:37]=3)[CH:22]=[CH:23][C:24]=2[CH3:25])[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 8471Triethylamine3×HCID 443297Hydroxyamine hydrochloride3×HCID 516892Sodium BicarbonateHCID 22050332ethyl 3-{3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylphenyl}-3-oxopropanoate

Product 1

HCID 178423845HCID 178423845, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of ethyl 3-{3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylphenyl}-3-oxopropanoate (0.20 g, 0.37 mmol), triethylamine (0.06 mL, 0.41 mmol), and hydroxylamine hydrochloride (0.03 g, 0.41 mmol) in EtOH (3.00 mL) was heated overnight at 60° C. with a condenser. Additional triethylamine (0.06 mL) and hydroxylamine hydrochloride (0.03 g) were added. After 2.5 h, the additions of triethylamine and hydroxylamine hydrochloride were repeated. After 1 h, the reaction was concentrated and purified by preparatory HPLC. The product was isolated by freeze-drying and evaporation of the solvent to give a white solid. Dissolved solid in DCM. Upon addition of 5% NaHCO3, solution became a milky emulsion. Added additional DCM and some brine. Organic extracts were dried over Na2SO4, filtered, and concentrated to a pink solid, dried in vacuo (120 mg, 64%). 1H NMR (CD3OD/400 MHz) δ 7.66 (m, 2H), 7.44 (m, 2H), 7.04 (t, 2H, J=8.8 Hz), 6.64 (s, 1H), 5.36 (s, 2H), 2.04 (s, 3H), 2.01 (s, 3H). ES HRMS m/z 503.0415 and 505.0402 (M+H calculated for C23H18BrF2N2O4 requires 503.0413 and 505.0395).

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction was concentrated
  3. custompurified by preparatory HPLC
  4. customThe product was isolated
  5. customby freeze-drying
  6. customevaporation of the solvent
  7. customto give a white solid
  8. dry with materialOrganic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to a pink solid
  11. customdried in vacuo (120 mg, 64%)

Sources & evidence

ORD record
ord-f7d76025898644e1b90fef591f6254f8
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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