Potassium Acetate → HCID 85095212, compound

HRID 1968687Notes

Reaction equation

HRID 1968687 reaction equation
[CH:1]1([C:4]([C:6]2[C:14]3[N:13]=[C:12]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[NH:11][C:10]=3[CH:9]=[C:8]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:7]=2)=O)[CH2:3][CH2:2]1.C([O-])(=O)C.[K+].Cl.[O:33]([NH2:35])[CH3:34]>CCO.CCOC(C)=O.O>[CH:1]1([C:4](=[N:35][O:33][CH3:34])[C:6]2[C:14]3[N:13]=[C:12]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[NH:11][C:10]=3[CH:9]=[C:8]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 521874O-Methylhydroxylamine hydrochlorideHCID 104730051-(4-cyclopropanecarbonyl-6-pyridin-3-yl-1H-benzoimidazol-2-yl)-3-ethyl-urea

Product 1

HCID 85095212HCID 85095212, compoundYield 27.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(4-cyclopropanecarbonyl-6-pyridin-3-yl-1H-benzoimidazol-2-yl)-3-ethyl-urea (37.2 g, 0.106 mmol) in dry EtOH (3 mL) were added potassium acetate (84 mg, 0.848 mmol, 8 eq.), methoxylamine hydrochloride (70.8 mg, 0.848 mmol, 8 eq.), molecular sieves (4 Å, powdered) in succession. The resulting suspension was stirred at 50° C. for 36 hours. The reaction mixture was then cooled to ambient temperature, diluted with EtOAc and water. The phases were separated, the aqueous layer was extracted with EtOAc (1×) and the combined organic extracts were dried (MgSO4), filtered, and the filtrate concentrated in vacuo. The residue was purified by preparative HPLC, converted to the bis-HCl salt to afford the title compound as a tan solid (11.0 mg): HPLC (10 to 90% CH3CN, 8 min.): tR=4.05 minutes; 1H NMR (CD3OD, 500 MHz) δ 9.30 (s, 1H), 8.99 (d, 1H), 8.90 (d, 1H), 8.22 (dd, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 4.14 (s, 3H), 3.36 (q, 2H), 2.04 (m, 1H), 1.23 (t, 3H), 1.15 (m, 2H), 0.92 (m, 2H); MS (ES+) m/z (M++1) 379.2.

Workup

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted with EtOAc (1×)
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-29f72a3361bb44379e40c82525496d79
Source dataset
uspto-grants-2013_04
Patent number
US08426426B2

Reaction notes

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