3-Aminopyridine → HCID 73052760, compound

HRID 1048726Notes

Reaction equation

HRID 1048726 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[N:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]3=[N:13][C:12]=2[CH2:20][S:21][CH2:22][C:23](O)=[O:24])[CH:6]=[CH:7][CH:8]=1.C(Cl)(=O)C(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+].[NH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1>ClCCl.O.CN(C=O)C>[N:43]1[CH:44]=[CH:45][CH:46]=[C:41]([NH:40][C:23](=[O:24])[CH2:22][S:21][CH2:20][C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]3[C:11]=2[C:10]#[C:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:26])([F:1])[F:27])[CH:4]=2)[CH:42]=1

Participants

8

Reactant 4

HCID 100093-AminopyridineHCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 73052449HCID 73052449, compound

Product 1

HCID 73052760HCID 73052760, compoundYield 53.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

141 mg (0.358 mmol) of 2-((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]-pyridin-2-yl)methylthio)acetic acid were dissolved in 5 ml of dichloromethane followed by the addition of 0.094 ml (1.073 mmol) of oxalyl chloride and a drop of DMF. The solvent was stirred at r.t. for 2 h and then the solvent was evaporated in vacuo. The obtained residue was taken up in 5 ml of tetrahydrofurane, 99 mg (0.715 mmol) of sodium carbonate were added followed by the addition of 40.4 mg (0.429 mmol) of 3-aminopyridine. The solution was stirred at r.t. for 16 h. The mixture was then poured onto 15 ml of water, extracted 3 times with 15 ml of ethyl acetate, the combined organic phases were washed with 20 ml of brine and then were dried on Na2SO4 which was then removed by filtration and the obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol gradient, 100% to 90% of dichloromethane, v/v). 89 mg of N-(pyridin-3-yl)-2-((3-((3-(trifluoromethyl)-phenyl)-ethynyl)imidazo[1,2-a]pyridin-2-yl)methylthio) acetamide were obtained as a pale yellow solid. LC-MS: m/z=467 (MH+) UV purity at 254 nm=95%. 1H NMR (300 MHz, DMSO) δ 10.13 (s, 1H), 8.76 (dd, J=16.4, 4.5 Hz, 2H), 8.24 (dd, J=4.7, 1.5 Hz, 1H), 8.07 (ddd, J=8.3, 2.5, 1.5 Hz, 1H), 7.79-7.60 (m, 3H), 7.60-7.35 (m, 3H), 7.30 (dd, J=8.3, 4.7 Hz, 1H), 7.16 (td, J=6.8, 1.1 Hz, 1H), 4.90 (s, 2H), 4.26 (s, 2H).

Workup

  1. customthe solvent was evaporated in vacuo
  2. stirringThe solution was stirred at r.t. for 16 h
  3. extractionextracted 3 times with 15 ml of ethyl acetate
  4. washthe combined organic phases were washed with 20 ml of brine
  5. customwere dried on Na2SO4 which
  6. customwas then removed by filtration
  7. concentrationthe obtained filtrate was concentrated in vacuo
  8. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol gradient, 100% to 90% of dichloromethane, v/v)

Sources & evidence

ORD record
ord-c70a886c8a6a420abf8b3f8cdf4c559b
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

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