Hydrochloric Acid → HCID 24961813, compound

HRID 1894179Notes

Reaction equation

HRID 1894179 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14]([C:17]4[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=4)=[CH:15][N:16]=[C:10]3[CH:9]=2)=[CH:4][CH:3]=1.Br[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1.Cl.CC([O-])(C)C.[Na+].N#N>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14]([C:17]4[CH:18]=[C:19]([NH:23][C:25]5[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=5)[CH:20]=[CH:21][CH:22]=4)=[CH:15][N:16]=[C:10]3[CH:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 142684-BromopyridineHCID 23676156Sodium t-butoxideHCID 59277797HCID 59277797, compound

Product 1

HCID 24961813HCID 24961813, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture 3-[7-(4-fluoro-phenyl)-imidazo[1,2-a]pyridin-3-yl]-phenylamine (200 mg, 0.65 mmol), 4-bromopyridine.HCl (130 mg, 0.67 mmol), (±)-Binap (63 mg, 0.1 mmol) and NaOtBu (250 mg, 2.6 mmol) in dry dioxane (3 ml) was deoxygenated by evacuation/refill with N2 (×3). Pd2(dba)3 (30 mg, 0.03 mmol) was added and the mixture was deoxygenated again (×3). The reaction was stirred and heated at 100° C. for 18 hours under N2. The mixture was partitioned between CH2Cl2/H2O, then filtered. The layers were separated and the solid was combined with the organic layer, which was then evaporated. The residue was purified by chromatography on silica followed by preparative HPLC to give the title compound (40 mg, solid). 1H NMR (400 MHz, Me-d3-OD): 8.63 (1H, d), 8.44 (1H, s), 8.22 (2H, d), 7.87-7.79 (4H, m), 7.70 (1H, t), 7.63-7.59 (2H, m), 7.48-7.43 (1H, m), 7.37 (1H, dd), 7.31-7.24 (2H, m), 7.17 (2H, d).

Workup

  1. customthe mixture was deoxygenated again (×3)
  2. customThe mixture was partitioned between CH2Cl2/H2O
  3. filtrationfiltered
  4. customThe layers were separated
  5. customwas then evaporated
  6. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-9a384f340a5f4fa3b1b10fafd3da5ad7
Source dataset
uspto-grants-2013_08
Patent number
US08513276B2

Reaction notes

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