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

HRID 869998Notes

Reaction equation

HRID 869998 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[C:23]([O:28]C)=[N:24][CH:25]=[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[C:23](=[O:28])[NH:24][CH:25]=[CH:26][CH:27]=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 687234901-(2,3-Dihydrobenzofuran-5-yl)-n-(2'-methoxy-3-methyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 687404681-(2,3-Dihydrobenzofuran-5-yl)-n-(5-methyl-6-(2-oxo-1,2-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamideYield 34.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To 1-(2,3-dihydrobenzofuran-5-yl)-N-(2′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (87 mg, 0.2 mmol) in 1,4-dioxane (1 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. The organics were dried over sodium sulfate and evaporated to dryness to yield the product (27 mg, 32%) ESI-MS m/z calc. 387.43. found 388.5 (M+1)+. Retention time 1.23 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.81 (s, 1H), 8.02 (s, 1H), 7.94 (d, J=8.3 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.45 (m, 1H), 7.37-7.35 (m, 2H), 7.24 (m, 1H), 6.80 (d, J=8.2 Hz, 1H), 6.24 (m, 1H), 4.54 (t, J=8.7 Hz, 2H), 3.19 (t, J=8.7 Hz, 2H), 2.07 (s, 3H), 1.50-1.47 (m, 2H), 1.11-1.08 (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
  7. dry with materialThe organics were dried over sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-a6e26acc350942e3b59b622b90f0aa60
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

Loading…