Methanol → HCID 67995133, compound

HRID 2361387Notes

Reaction equation

HRID 2361387 reaction equation
Cl[C:2]1[C:7]2[NH:8][C:9]3[CH:10]=[C:11]([C:15](=[O:17])[CH3:16])[CH:12]=[CH:13][C:14]=3[C:6]=2[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([N+:24]([O-])=O)[C:19]=2[CH3:27])=[N:4][N:3]=1.[CH3:28]O.[C:30]([O-:33])(=[O:32])C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO.C(Cl)Cl>[C:15]([C:11]1[CH:12]=[CH:13][C:14]2[C:6]3[C:5]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH2:24])[C:19]=4[CH3:27])=[N:4][N:3]=[C:2]([C:30]([O:33][CH3:28])=[O:32])[C:7]=3[NH:8][C:9]=2[CH:10]=1)(=[O:17])[CH3:16]

Participants

7

Reactant 3

HCID 887MethanolHCID 517045Sodium AcetateHCID 86681526HCID 86681526, compound

Product 1

HCID 67995133HCID 67995133, compoundYield 60.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
95 °C

Procedure

1-(4-Chloro-1-(2-methyl-3-nitrophenyl)-5H-pyridazino[4,5-b]indol-7-yl)ethanone (0.90 g, 2.364 mmol), methanol (30 mL, 740 mmol), DPPF (0.197 g, 0.355 mmol), palladium (II) acetate (0.080 g, 0.355 mmol), and sodium acetate (0.388 g, 4.73 mmol) were placed into a steel bomb. The bomb was evacuated and refilled with nitrogen. This operation was once repeated. The bomb was vacuumed again and then charged with CO (g) at 50 psi. The bomb was then heated at 95° C. for 20 hr. Upon cooling to room temperature, the bomb was further cooled at −78° C. and the excess CO (g) was released. The reaction mixture was diluted with ethyl acetate (20 mL) and filtered through CELITE®. The filtrate was concentrated under vacuum. The residue was diluted with ethyl acetate (180 mL), washed with water (2×40 mL) and brine (40 mL), and dried over anhydrous. The desired product, methyl 7-acetyl-1-(3-amino-2-methylphenyl)-5H-pyridazino[4,5-b]indole-4-carboxylate (0.539 g, 1.440 mmol, 60.9% yield), was isolated as a beige solid by ISCO (120 g silica gel, 1-5% methanol/CH2Cl2).

Workup

  1. customThe bomb was evacuated
  2. additionrefilled with nitrogen
  3. additioncharged with CO (g) at 50 psi
  4. temperatureUpon cooling to room temperature
  5. temperaturethe bomb was further cooled at −78° C.
  6. additionThe reaction mixture was diluted with ethyl acetate (20 mL)
  7. filtrationfiltered through CELITE®
  8. concentrationThe filtrate was concentrated under vacuum
  9. additionThe residue was diluted with ethyl acetate (180 mL)
  10. washwashed with water (2×40 mL) and brine (40 mL)
  11. customdried over anhydrous

Sources & evidence

ORD record
ord-1703dc310dce45d69a713800187d1e04
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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