Ethyl Acetate → HCID 57791842, compound

HRID 1091778Notes

Reaction equation

HRID 1091778 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:23])[NH:7][N:8]=[C:9]2[CH2:12][C:13]2[CH:14]=[CH:15][C:16]([F:22])=[C:17]([CH:21]=2)[C:18]([OH:20])=O)=[CH:4][CH:3]=1.[CH3:24][O:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.C(OCC)(=O)C>CN(C=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][CH:3]=1)[C:6](=[O:23])[NH:7][N:8]=[C:9]2[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17]([C:18]([N:29]2[CH2:30][CH2:31][CH:26]([O:25][CH3:24])[CH2:27][CH2:28]2)=[O:20])[CH:21]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 776664-MethoxypiperidineHCID 81531DiisopropylethylamineHCID 57791829HCID 57791829, compound

Product 1

HCID 57791842HCID 57791842, compoundYield 5.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-((7-bromo-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-2-fluorobenzoic acid (97) (1.0 g, 2.65 mmol), 4-methoxypiperidine (0.336 g, 2.92 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.936 g, 2.92 mmol) were dissolved in DMF (40 mL), to this was added DIPEA (0.509 mL, 2.92 mmol) and the reaction was stirred for 1 hour. The DMF was evaporated and the crude gum was quenched with 2M NaOH (75 mL), extracted with EtOAc (3×75 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford a brown gum. The gum was passed through a plug of silica eluting with ethyl acetate to afford a white solid, most of which was used without further purification. A sample (100 mg) was purified via preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (66 mg); 1H NMR (400.132 MHz, CDCl3) δ 1.62-1.48 (1H, m), 1.85-1.68 (2H, m), 1.94-1.89 (1H, m), 3.18-3.07 (1H, m), 3.35 (3H, s), 3.47-3.40 (2H, m), 3.67-3.53 (1H, m), 4.06-3.89 (1H, m), 4.23 (2H, s), 7.04 (1H, t), 7.31-7.26 (2H, m), 7.86-7.84 (2H, m), 8.33-8.31 (1H, m), 10.55 (1H, s); m/z (LC-MS, ESI+), RT=1.94 (M+H 476).

Workup

  1. customThe DMF was evaporated
  2. customthe crude gum was quenched with 2M NaOH (75 mL)
  3. extractionextracted with EtOAc (3×75 mL)
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a brown gum
  8. customto afford a white solid
  9. custommost of which was used without further purification
  10. customA sample (100 mg) was purified via preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-e4caaacbaee24955943e92e5929c0b54
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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