Acetic Acid → HCID 117926313, compound

HRID 1054203Notes

Reaction equation

HRID 1054203 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[N:18]=[CH:17][CH:16]=[CH:15][C:10]=1[C:11]([O:13]C)=O)=O.Cl.Cl.[CH2:21]([NH:28][NH2:29])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(C(C)C)CC)(C)C.C(O)(=O)C>C(O)C>[CH2:21]([N:28]1[C:11](=[O:13])[C:10]2[CH:15]=[CH:16][CH:17]=[N:18][C:9]=2[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[N:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 146540Benzylhydrazine dihydrochlorideHCID 117925708HCID 117925708, compound

Product 1

HCID 117926313HCID 117926313, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of methyl 2-picolinoyl nicotinate, compound 6, (130 mg, 0.54 mmol), benzylhydrazine dihydrochloride (146 mg, 0.81 mmol), diisopropylethylamine (104 mg, 0.81 mmol), and ethanol (5 mL) was heated overnight at 75° C. To the reaction mixture was added acetic acid (46 μL, 0.81 mmol). The reaction mixture was heated at 75° C. for 2 h and then 100° C. for 2 h. After cooling the excess solvent was removed under reduced pressure. The residue was partitioned between 15 mL of ethyl acetate and 10% aqueous sodium carbonate. The aqueous fraction was further extracted with 2×15 mL of ethyl acetate. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by normal phase flash chromatography eluting with 0-5% methanol in dichloromethane over 20 minutes. Like fractions containing product were combined and concentrated under reduced pressure to give 6-benzyl-8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one, RL-10 (44 mg, 0.13 mmol). 1H NMR (400 MHz, Chloroform-d) δ 9.11 (dd, J=4.5, 1.8 Hz, 2H), 8.89 (d, J=3.9 Hz, 2H), 8.77 (dd, J=8.1, 1.8 Hz, 1H), 7.91 (s, 2H), 7.68 (dd, J=8.1, 4.5 Hz, 1H), 7.49 (dd, J=25.2, 5.7 Hz, 3H), 7.37-7.24 (m, 5H), 5.53 (s, 2H). LCMS: (M+H)+, 316.

Workup

  1. temperatureThe reaction mixture was heated at 75° C. for 2 h
  2. temperatureAfter cooling the excess solvent
  3. customwas removed under reduced pressure
  4. customThe residue was partitioned between 15 mL of ethyl acetate and 10% aqueous sodium carbonate
  5. extractionThe aqueous fraction was further extracted with 2×15 mL of ethyl acetate
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by normal phase flash chromatography
  10. washeluting with 0-5% methanol in dichloromethane over 20 minutes
  11. additionLike fractions containing product
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7ef3557a92ed48cd94181a1b0b57778d
Source dataset
uspto-grants-2016_07
Patent number
US09394299B2

Reaction notes

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