Triethylamine → HCID 22051033, compound

HRID 1867143Notes

Reaction equation

HRID 1867143 reaction equation
[Br:1][C:2]1[C:3](=[O:29])[N:4]([CH2:19][C:20]2[CH:25]=[N:24][C:23]([CH2:26][NH:27][CH3:28])=[CH:22][N:21]=2)[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([O:33][C:34]([CH3:39])([CH3:38])[C:35](Cl)=[O:36])(=O)C.C(N(CC)CC)C>CN(C=O)C>[Br:1][C:2]1[C:3](=[O:29])[N:4]([CH2:19][C:20]2[N:21]=[CH:22][C:23]([CH2:26][N:27]([CH3:28])[C:35](=[O:36])[C:34]([OH:33])([CH3:38])[CH3:39])=[N:24][CH:25]=2)[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

5

Reactant 3

HCID 8471TriethylamineHCID 1234962-Acetoxyisobutyroyl chlorideHCID 22050409HCID 22050409, compound

Product 1

HCID 22051033HCID 22051033, compoundYield 26.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (5° C.) solution of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-1-({5-[(methylamino)methyl]pyrazin-2-yl}methyl)pyridin-2(1H)-one (0.24 g, 0.52 mmol) in DMF (2.0 ml), was added 2-acetoxyisobutyryl chloride (0.093 g, 0.56 mmol), followed by the addition of triethylamine (0.072 g, 0.71 mmol). The mixture was stirred at room temperature for an additional 2 h and concentrated in vacuo. The residue was partitioned between water (5.0 mL) and EtOAc (15.0 mL). The EtOAc extract was washed with water, dried (Na2SO4), and concentrated to dryness. The resulting material (0.2 g) was stirred with 1M. LiOH (0.5 mL, MeOH,/Water 1:1 v/v) at room temperature for 3 h, cooled, acidified with trifluoroacetic acid and the product was purified by reverse-phase HPLC using 10-90% CH3CN/Water gradient (60 min) at a flow rate of 70 mL/min. The appropriate fractions (m/z=551 M+H) were combined and freeze dried to give a white powder. This was partitioned between 5% NaHCO3 (10 mL) and EtoAc (15 mL). The organic layer was washed with water, dried (Na2SO4), and concentrated to dryness to afford the title compound (0.075 g) as a white powder: 1H NMR (CD3OD/400 MHz) δ 8.59 (s, 1H), 8.41 (br, 1H), 7.60 (m, 2H), 7.01 (m, 2H), 6.52 (s, 1H), 5.45 (s, 2 h), 5.29 (s, 2H),

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between water (5.0 mL) and EtOAc (15.0 mL)
  3. extractionThe EtOAc extract
  4. washwas washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to dryness
  7. stirringThe resulting material (0.2 g) was stirred with 1M
  8. waitLiOH (0.5 mL, MeOH,/Water 1:1 v/v) at room temperature for 3 h
  9. temperaturecooled
  10. customthe product was purified by reverse-phase
  11. custom10-90% CH3CN/Water gradient (60 min)
  12. customfreeze dried
  13. customto give a white powder
  14. customThis was partitioned between 5% NaHCO3 (10 mL) and EtoAc (15 mL)
  15. washThe organic layer was washed with water
  16. dry with materialdried (Na2SO4)
  17. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-045aab2f5f184d8eaa27c515f793b9ac
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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