HCID 68157292, compound → HCID 68157795, compound

HRID 243434Notes

Reaction equation

HRID 243434 reaction equation
[NH2:1][C:2]1[C:3](Cl)=[C:4]([NH:10][C@H:11]([C:13]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:16]3[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:15]=3[N:14]=2)[CH3:12])[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1>C(OCC)(=O)C.C(=O)([O-])O.[Na+].[Pd]>[NH2:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([C:13]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:16]3[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:15]=3[N:14]=2)[CH3:12])[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Participants

5

Reactant 1

HCID 68157292HCID 68157292, compound

Product 1

HCID 68157795HCID 68157795, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

6-Amino-5-chloro-4-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamino]-2-methyl-2H-pyridazin-3-one (0.13 g, 0.315 mmol) in ethyl acetate (10 mL) and sat. aq sodium hydrogen carbonate (1 mL) was hydrogenated over 10% palladium on carbon (40 mg) at room temperature and pressure for 24 h. The reaction mix was filtered, evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-5% (9:1 MeOH/0.880 NH3) in DCM). Fractions containing the product were evaporated and freeze dried to give 344 as a white solid, (77 mg, 64%). LCMS (Method C): RT 3.57 min [M+H]+ 379.05. 1H NMR δ (ppm DMSO-d6): 7.76 (1H, dd, J=8.82, 4.84 Hz), 7.63-7.62 (5H, m), 7.14 (1H, ddd, J=9.9, 8.9, 2.5 Hz), 6.87 (1H, dd, J=8.88, 2.51 Hz), 6.47 (1H, d, J=7.48 Hz), 5.44 (1H, s), 5.18 (2H, s), 4.62 (1H, dq, J=6.95 Hz), 3.40 (3H, s), 1.41 (3H, d, J=6.63 Hz)

Workup

  1. additionThe reaction mix
  2. filtrationwas filtered
  3. customevaporated to dryness
  4. custompurified by column chromatography (Si—PCC, gradient 0-5% (9:1 MeOH/0.880 NH3) in DCM)
  5. additionFractions containing the product
  6. customwere evaporated
  7. customfreeze dried

Sources & evidence

ORD record
ord-d52f5efed9de485c968729c761fc7e75
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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