6-Aminopyridine-3-thiol → HCID 178428244, compound

HRID 499095Notes

Reaction equation

HRID 499095 reaction equation
[CH:1]1([C:4]2([F:25])[CH2:7][N:6]([C:8]3[N:13]=[C:12]([S:14]([CH3:17])(=O)=O)[N:11]=[C:10]([NH:18][C:19]4[NH:23][N:22]=[C:21]([CH3:24])[CH:20]=4)[CH:9]=3)[CH2:5]2)[CH2:3][CH2:2]1.[NH2:26][C:27]1[N:32]=[CH:31]C(S)=[CH:29][CH:28]=1>CN(C=O)C.C(OC(=O)C)C.C([O-])(O)=O.[Na+]>[NH2:26][C:27]1[N:32]=[CH:31][C:17]([S:14][C:12]2[N:11]=[C:10]([NH:18][C:19]3[NH:23][N:22]=[C:21]([CH3:24])[CH:20]=3)[CH:9]=[C:8]([N:6]3[CH2:7][C:4]([CH:1]4[CH2:3][CH2:2]4)([F:25])[CH2:5]3)[N:13]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 2

HCID 14158806-Aminopyridine-3-thiolHCID 1784282456-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine

Product 1

HCID 178428244HCID 178428244, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 6-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine (880 mg, 2.4 mmol) and 6-aminopyridine-3-thiol) (300 mg, 2.4 mmol) in DMF (10 ml) was heated to 80° C. and stirred for 2 hrs. The reaction was diluted with ethylacetate (150 ml) and Sat. NaHCO3 (50 ml) and the organic layer washed with brine (50 ml), dried (MgSO4) and concentrated to give an oil. The residue was purified by flash column chromatography eluting with Pentane/EtOAc (5% MeOH) 0 to 100%. The resulting compound was triturated in 10:1 DCM:MeOH and filtered to give the title compound as a white solid (300 mg, 30%). 1H NMR (DMSO, 400 MHz) 0.42-0.44 (2H, m), 0.55-0.60 (2H, m), 1.35-1.45 (1H, m), 2.11 (3H, s), 3.81-3.90 (4H, m), 5.55-5.80 (2H, m), 6.35 (2H, s), 6.49-6.52 (1H, d), 7.46-7.49 (1H, d), 7.97 (1H, s), 9.30-9.35 (1H, s). ES+ 413

Workup

  1. washthe organic layer washed with brine (50 ml)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customto give an oil
  5. customThe residue was purified by flash column chromatography
  6. washeluting with Pentane/EtOAc (5% MeOH) 0 to 100%
  7. customThe resulting compound was triturated in 10:1 DCM
  8. filtrationMeOH and filtered

Sources & evidence

ORD record
ord-94250cfa075443ff9c9ff292f589fb98
Source dataset
uspto-grants-2010_08
Patent number
US07767672B2

Reaction notes

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