Diisopropylethylamine → HCID 60162558, compound

HRID 243425Notes

Reaction equation

HRID 243425 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[C:24](=[O:31])[N:25]([CH3:30])[N:26]=[CH:27][C:28]=1[Cl:29].C(N(C(C)C)CC)(C)C>C(O)(C)C.CCOC(C)=O>[Cl:29][C:28]1[CH:27]=[N:26][N:25]([CH3:30])[C:24](=[O:31])[C:23]=1[NH:14][C@H:12]([C:10]1[N:9]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:8]2[CH:21]=[C:4]([F:3])[CH:5]=[CH:6][C:7]=2[N:11]=1)[CH3:13]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1204623(2H)-Pyridazinone, 4,5-dichloro-2-methyl-HCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 60162558HCID 60162558, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (1.0 g, 3.05 mmol), 4,5-dichloro-2-methyl-2H-pyridazin-3-one (J. Org. Chem. 2473-76, 46, 1981) (0.546 g, 3.05 mmol) and diisopropylethylamine (2.1 mL, 12.8 mmol) in isopropanol (5 mL) was heated to reflux for 4.25 h then at 75° C. for 20 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with 1M sodium carbonate (10 mL). The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM then gradient 20-100% EtOAc in DCM). Fractions containing the less polar product were evaporated and freeze dried to give 323 as a yellow solid, (78 mg, 6.4%). LCMS (Method C): RT 4.80 min [M+H]+ 398.00. 1H NMR δ (ppm) (DMSO-d): 7.77 (1H, dd, J=8.82, 4.85 Hz), 7.56-7.55 (6H, m), 7.14 (1H, ddd, J=9.9, 8.9, 2.50 Hz), 6.89 (1H, dd, J=8.91, 2.51 Hz), 6.61 (1H, d, J=9.09 Hz), 5.94 (1H, t, J=7.66 Hz), 3.56 (3H, s), 1.51 (3H, d, J=6.65 Hz)

Workup

  1. temperatureto reflux for 4.25 h
  2. temperatureThe reaction mixture was cooled
  3. washwashed with 1M sodium carbonate (10 mL)
  4. dry with materialThe organic extracts were dried (Na2SO4)
  5. customevaporated to dryness
  6. custompurified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM
  7. additionFractions containing the less polar product
  8. customwere evaporated
  9. customfreeze dried

Sources & evidence

ORD record
ord-60c9ae7dddd346d186254d86026bda08
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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