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

HRID 474023Notes

Reaction equation

HRID 474023 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-363a472d8dc9496d99a4ec63cf874603
Source dataset
uspto-grants-2014_01
Patent number
US08637511B2

Reaction notes

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