Ethyl Bromide → HCID 117925976, compound

HRID 1054205Notes

Reaction equation

HRID 1054205 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:12]2[N:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C:10](=[O:17])[NH:9][N:8]=1.[CH2:18](Br)[CH3:19].C(=O)([O-])[O-].[K+].[K+].C1C(O)=CC(O)=C(C2C(=O)C3C(=CC(O)=C(CC=C(CO)CO)C=3O)OC=2)C=1>[Cl-].[Na+].O.CN(C)C=O>[CH2:18]([N:9]1[C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[N:13][C:12]=2[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[N:8]1)[CH3:19]

Participants

7

Reactant 4

HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 66966126HCID 66966126, compoundHCID 101613216HCID 101613216, compound

Product 1

HCID 117925976HCID 117925976, compoundYield 86.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one 8 (50 mg, 0.22 mmol), ethyl bromide (20 μL, 0.27 mmol), potassium carbonate (303 mg, 2.2 mmol), and dimethylformamide (1.5 mL) was heated in a sealed tube at 60° C. for 30 minutes. After cooling to ambient temperature, the reaction mixture was poured into 15 mL of saturated brine and extracted with 3×20 mL of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase flash chromatography eluting with 0-10% methanol in dichloromethane over 16 minutes Like fractions containing product were pooled, concentrated under reduced pressure, and dried at 60° C. overnight to give 6-ethyl-8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one (46 mg, 0.19 mmol), RL-6. 1H NMR (400 MHz, Chloroform-d) δ 9.15 (s, 1H), 9.02 (s, 1H), 8.80 (d, J=8.3 Hz, 1H), 8.23 (s, 1H), 8.04 (s, 1H), 7.71 (dd, J=8.1, 4.6 Hz, 1H), 7.56 (s, 1H), 4.48 (q, J=7.1 Hz, 2H), 1.52 (t, J=7.2 Hz, 3H). LCMS: (M+H)+, 253.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with 3×20 mL of ethyl acetate
  3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by normal phase flash chromatography
  7. washeluting with 0-10% methanol in dichloromethane over 16 minutes Like fractions
  8. additioncontaining product
  9. concentrationconcentrated under reduced pressure
  10. customdried at 60° C. overnight

Sources & evidence

ORD record
ord-8c27c92fe9d643638860ded7ac9c7e20
Source dataset
uspto-grants-2016_07
Patent number
US09394299B2

Reaction notes

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