Diisopropylethylamine → HCID 68157292, compound

HRID 243433Notes

Reaction equation

HRID 243433 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.[NH2:22][C:23]1[C:24]([Cl:32])=[C:25](Cl)[C:26](=[O:30])[N:27]([CH3:29])[N:28]=1.C(N(C(C)C)CC)(C)C>C(O)CCC.CCOC(C)=O>[NH2:22][C:23]1[C:24]([Cl:32])=[C:25]([NH:14][C@H:12]([C:10]2[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]3[CH:21]=[C:4]([F:3])[CH:5]=[CH:6][C:7]=3[N:11]=2)[CH3:13])[C:26](=[O:30])[N:27]([CH3:29])[N:28]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 108216203(2H)-Pyridazinone, 6-amino-4,5-dichloro-2-methyl-HCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 68157292HCID 68157292, compoundYield 13.3%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (1.0 g, 3.05 mmol), 6-amino-4,5-dichloro-2-methyl-2H-pyridazin-3-one (J. Het Chem, 5-10 37, 2000) (0.59 g, 3.05 mmol) and diisopropylethylamine (2.1 mL, 12.8 mmol) in butanol (5 mL) was heated to 115° C. in a sealed tube under argon for 19 h. The reaction mixture was cooled and diluted with EtOAc (50 mL) and washed with water (20 mL). The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 1-8% (9:1 MeOH/0.880 NH3) in DCM then gradient 20-100% EtOAc in cyclohexane). Fractions containing the less polar product were evaporated and freeze dried to give 341 as a yellow solid, (167 mg, 13%). LCMS (Method C): RT 4.01 min [M+H]+ 313.02. 1H NMR δ (ppm DMSO-d6): 7.76 (1H, dd, J=8.81, 4.85 Hz), 7.56-7.40 (5H, m), 7.13 (1H, ddd, J=9.85, 8.80, 2.53 Hz), 6.88 (1H, dd, J=8.91, 2.51 Hz), 5.70 (1H, d, J=9.37 Hz), 5.61-5.60 (1H, m), 5.52 (2H, s), 3.37 (3H, s), 1.59 (3H, d, J=6.56 Hz)

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with water (20 mL)
  3. dry with materialThe organic extracts were dried (Na2SO4)
  4. customevaporated to dryness
  5. custompurified by column chromatography (Si—PCC, gradient 1-8% (9:1 MeOH/0.880 NH3) in DCM
  6. additionFractions containing the less polar product
  7. customwere evaporated
  8. customfreeze dried

Sources & evidence

ORD record
ord-fd05e5b9a4de49c8bdddef8e0119591f
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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