Sulfuric Acid → HCID 86715527, compound

HRID 2284611Notes

Reaction equation

HRID 2284611 reaction equation
OS(O)(=O)=O.C(O)(C(F)(F)F)=[O:7].[Cl:13][C:14]1[CH:15]=[C:16]([C:21]2[C:26]([C:27]3[CH:28]=[CH:29][C:30]4[N:31]([C:33]([C:36]#[N:37])=[CH:34][N:35]=4)[CH:32]=3)=[CH:25][CH:24]=[CH:23][N:22]=2)[CH:17]=[CH:18][C:19]=1[F:20].[OH-].[Na+]>>[Cl:13][C:14]1[CH:15]=[C:16]([C:21]2[C:26]([C:27]3[CH:28]=[CH:29][C:30]4[N:31]([C:33]([C:36]([NH2:37])=[O:7])=[CH:34][N:35]=4)[CH:32]=3)=[CH:25][CH:24]=[CH:23][N:22]=2)[CH:17]=[CH:18][C:19]=1[F:20]

Participants

5

Reactant 4

HCID 1118Sulfuric Acid2×HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 86715528HCID 86715528, compound

Product 1

HCID 86715527HCID 86715527, compound

Procedure

Conc. H2SO4 was added dropwise to stirring TFA at room temperature for 5 min. 6-(2-(3-Chloro-4-fluorophenyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carbonitrile (870 mg) was added all at once to the homogenous solution after fuming subsided from acid mixture. Additional TFA and conc. H2SO4 were added successively to the heterogeneous reaction mixture. After 6 h, the reaction mixture was added to ice/water and stirred. The homogeneous solution was basified with aq. NaOH (50%). The resultant heterogeneous slurry was filtered and dried. Subsequently, the white solid was purified by flash chromatography (Combiflash® companion System® with RediSep® silica gel column 24 g, 70% EtOAc/hexanes-3% MeOH/EtOH) to obtain 6-(2-(3-chloro-4-fluorophenyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide (720 mg). 1H NMR (300 MHz, DMSO-d6): δ 9.48 (s, 1H), 8.72 (dd, J=4.8, 1.6 Hz, 1H), 8.33 (s, 1H), 7.97 (dd, J=7.8, 1.7 Hz, 2H), 7.64 (d, J=6.8 Hz, 1H), 7.61-7.57 (m, 1H), 7.55 (dd, J=7.9, 4.9 Hz, 1H), 7.52-7.48 (br s, 2H), 7.26 (dd, J=7.7, 1.5 Hz, 1H), 7.10 (dd, J=9.4, 1.9 Hz, 1H). 19F NMR (282 MHz, DMSO-d6): δ −117.01 (q, J=7.5, 7.1 Hz). LCMS: rt 4.65 min (A), purity 99%, MS (m/e) 367 MH+.

Workup

  1. filtrationThe resultant heterogeneous slurry was filtered
  2. customdried
  3. customSubsequently, the white solid was purified by flash chromatography (Combiflash® companion System® with RediSep® silica gel column 24 g, 70% EtOAc/hexanes-3% MeOH/EtOH)

Sources & evidence

ORD record
ord-4bd2ac550e7f4018be8d2a71394c0cf3
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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