Hydrochloric Acid → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-4-(6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)cyclopropanecarboxamide

HRID 2401962Notes

Reaction equation

HRID 2401962 reaction equation
[F:1][C:2]1([F:32])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([O:29]C)=[CH:27][CH:28]=5)[C:20]([CH3:31])=[CH:19][N:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.Cl>O1CCOCC1>[F:32][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:28]=[CH:27][C:26](=[O:29])[NH:25][CH:24]=5)[C:20]([CH3:31])=[CH:19][N:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 578561031-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-yl)cyclopropanecarboxamide

Product 1

HCID 578561171-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-4-(6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-(6-methoxypyridin-3-yl)-5-methylpyrimidin-2-yl)cyclopropanecarboxamide (126 mg, 0.286 mmol) in 1,4-dioxane (1.50 mL), 4 M aqueous HCl (775 μL, 3.10 mmol) was added and stirred at 90° C. for one hour. The reaction was cooled to room temperature, quenched with Et3N and concentrated. The resulting mixture was dissolved in EtOAc and filtered. The solid was dissolved in water and the product was extracted using ethyl acetate (×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was dissolved in DMSO (1 mL), filtered and purified by reverse phase preparative HPLC to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-4-(6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 426.11, found 427.3 (M+1)+. Retention time 1.34 minutes.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with Et3N
  3. concentrationconcentrated
  4. dissolutionThe resulting mixture was dissolved in EtOAc
  5. filtrationfiltered
  6. dissolutionThe solid was dissolved in water
  7. extractionthe product was extracted
  8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  9. customevaporated under reduced pressure
  10. dissolutionThe crude product was dissolved in DMSO (1 mL)
  11. filtrationfiltered
  12. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-129954f9d735452f89908b9f8e72b52c
Source dataset
uspto-grants-2014_08
Patent number
US08796312B2

Reaction notes

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