Hydrochloric Acid → 1-(2,3-Dihydrobenzofuran-5-yl)-n-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 869987Notes

Reaction equation

HRID 869987 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[N:21]=[C:20]([C:22]5[CH:23]=[N:24][C:25]([O:28]C)=[CH:26][CH:27]=5)[C:19]([CH3:30])=[CH:18][CH:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1.Cl>O1CCOCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[CH:18][C:19]([CH3:30])=[C:20]([C:22]5[CH:27]=[CH:26][C:25](=[O:28])[NH:24][CH:23]=5)[N:21]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 687235411-(2,3-Dihydrobenzofuran-5-yl)-n-(6'-methoxy-3-methyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 251187191-(2,3-Dihydrobenzofuran-5-yl)-n-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamideYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To 1-(2,3-dihydrobenzofuran-5-yl)-N-(6′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (72 mg, 0.18 mmol) in 1,4-dioxane (2 mL) was added 0.5 mL of an aqueous 4 M hydrochloric acid solution. The reaction mixture was heated to 90° C. for 30 minutes before being quenched with triethlyamine (0.5 mL) and evaporated to dryness. The residue was dissolved in N,N-dimethylformamide (1 mL) and purified by reverse-phase preparative liquid chromatography. The resulting trifluoroacetic acid salt was dissolved in dichloromethane (5 mL) and washed with a saturated sodium bicarbonate solution (5 mL). The organics were dried over sodium sulfate and evaporated to dryness to yield the product (30 mg, 44%) ESI-MS m/z calc. 387.43. found 388.3 (M+1)+. Retention time 1.39 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 8.18 (s, 1H), 7.89 (d, J=8.3 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.61-7.58 (m, 1H), 7.51 (m, 1H), 7.37 (m, 1H), 7.26-7.23 (m, 1H), 6.81 (d, J=8.2 Hz, 1H), 6.36 (d, J=9.5 Hz, 1H), 4.55 (t, J=8.7 Hz, 2H), 3.19 (t, J=8.7 Hz, 2H), 2.27 (s, 3H), 1.49-1.46 (m, 2H), 1.11-1.09 (m, 2H).

Workup

  1. custombefore being quenched with triethlyamine (0.5 mL)
  2. customevaporated to dryness
  3. dissolutionThe residue was dissolved in N,N-dimethylformamide (1 mL)
  4. custompurified by reverse-phase preparative liquid chromatography
  5. dissolutionThe resulting trifluoroacetic acid salt was dissolved in dichloromethane (5 mL)
  6. washwashed with a saturated sodium bicarbonate solution (5 mL)
  7. dry with materialThe organics were dried over sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-28fc9c9bb18341b2a98fda0b483ef389
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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