Dimethylformamide → HCID 90095144, compound

HRID 2284612Notes

Reaction equation

HRID 2284612 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[C:14]([C:15]3[CH:16]=[CH:17][C:18]4[N:19]([C:21]([C:24]([NH2:26])=O)=[CH:22][N:23]=4)[CH:20]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C[N:28]([CH:30]=O)C.CC([N:35](C)C)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[C:14]([C:15]3[CH:16]=[CH:17][C:18]4[N:19]([C:21]([C:24]5[NH:26][N:28]=[CH:30][N:35]=5)=[CH:22][N:23]=4)[CH:20]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 31374DimethylacetamideHCID 86715527HCID 86715527, compound

Product 1

HCID 90095144HCID 90095144, compound

Procedure

6-(2-(3-Chloro-4-fluorophenyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide (290 mg) and DMF.DMA (5 mL) were heated at 95° C. and stirred in a screw capped vial overnight. The pale yellow homogeneous reaction mixture was cooled to room temperature and concentrated the heterogeneous slurry by rotary evaporator under vacuum. The off-white solid residue was transferred to a screw capped vial, treated with AcOH (3 mL) dropwise for 3 min followed by N2H4.H2O (0.05 mL) and heated for 1 h at 90° C. The homogeneous reaction mixture was concentrated, diluted with ice/water and allowed the resulting suspension warm to room temperature. Upon filtration, the collected solid was neutralized with aq. NaHCO3 and filtered again to obtain 6-(2-(3-chloro-4-fluorophenyl)pyridin-3-yl)-3-(1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine as an off-white solid (220 mg). 1H NMR (300 MHz, DMSO-d6): δ 14.03 (br s, 1H), 9.46 (dd, J=1.9, 1.0 Hz, 1H), 8.79-8.70 (m, 1H), 8.70-8.52 (m, 1H), 8.18 (s, 1H), 8.02 (dd, J=7.8, 1.6 Hz, 1H), 7.67 (dd, J=6.2, 1.4 Hz, 1H), 7.61 (dd, J=9.3, 1.0 Hz, 1H), 7.56 (dd, J=7.8, 4.7 Hz, 1H), 7.28 (d, J=0.7 Hz, 1H), 7.27-7.20 (m, 1H), 7.04 (dd, J=9.3, 1.8 Hz, 1H). 19F NMR (282 MHz, DMSO-d6): δ −114.49-−119.56 (m). LCMS: rt 4.70 min (A), purity 99%, MS (m/e) 391 MH+.

Workup

  1. customcapped vial overnight
  2. concentrationconcentrated the heterogeneous slurry
  3. customby rotary evaporator under vacuum
  4. customcapped vial
  5. additiontreated with AcOH (3 mL) dropwise for 3 min
  6. temperatureheated for 1 h at 90° C
  7. concentrationThe homogeneous reaction mixture was concentrated
  8. additiondiluted with ice/water
  9. temperaturewarm to room temperature
  10. filtrationUpon filtration
  11. filtrationfiltered again

Sources & evidence

ORD record
ord-fafc65365361410ebc3844430a9d3dac
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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