2-Aminopyridine → 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

HRID 419300Notes

Reaction equation

HRID 419300 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](/[CH:8]=[C:9](\[C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[C:14]([NH:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[O:15])/O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[NH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[N:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]3=[N:36][C:9]=2[C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[C:14]([NH:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[O:15])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 104392-AminopyridineHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 136078482HCID 136078482, compound

Product 1

HCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamideYield 77%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A tautomeric mixture of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-fluorophenyl)benzamide and 3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]-N-(2,6-difluorophenyl)benzamide (5.73 g, 14.8 mmol) was dissolved in 150 mL of DCM with stirring. NBS (2.63 g, 14.8 mmol) was added in a single portion, and the reaction was stirred for 15 minutes. The reaction was concentrated in vacuo. Dioxane (100 mL) was added to dissolve the residue with stirring. 2-Aminopyridine (4.18 g, 44.4 mmol) was added, and the reaction was heated to 60° C. for 16 hours. The reaction was cooled to rt and poured into half-saturated NaHCO3 solution and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The mixture was purified by flash chromatography to afford 5.26 g (77%) of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.40 (d, J=7.0 Hz, 1H), 8.56 (d, J=5.3 Hz, 1H), 8.33 (s, 1H), 8.08 (d, J=7.9 Hz, 1H), 7.85 (d, J=7.9 Hz, 1H), 7.81 (d, J=9.0 Hz, 1H), 7.66-7.54 (m, 2H), 7.89 (m, 1H), 7.27-7.15 (m, 4H).

Workup

  1. stirringthe reaction was stirred for 15 minutes
  2. concentrationThe reaction was concentrated in vacuo
  3. additionDioxane (100 mL) was added
  4. dissolutionto dissolve the residue
  5. stirringwith stirring
  6. temperatureThe reaction was cooled to rt
  7. customThe layers were separated
  8. washthe organic layer was washed with brine
  9. extractionThe combined aqueous layers were extracted with EtOAc
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-cbea21bf54bc48dc816d5c83201f370b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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