Ammonium Chloride → HCID 178503416, compound

HRID 925416Notes

Reaction equation

HRID 925416 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[NH:13][N:12]=[C:11]([C:14]([OH:16])=O)[CH:10]=2)[CH:6]=[CH:5][N:4]=1.[O:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]1[O:23][NH2:24].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[NH:13][N:12]=[C:11]([C:14]([NH:24][O:23][CH:18]3[CH2:19][CH2:20][CH2:21][CH2:22][O:17]3)=[O:16])[CH:10]=2)[CH:6]=[CH:5][N:4]=1

Participants

10

Reactant 7

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 178503417HCID 178503417, compound

Product 1

HCID 178503416HCID 178503416, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

5-(2-methylsulfanyl-pyrimidin-4-yl)-1H-pyrazole-3-carboxylic acid (60 mg, 0.25 mmol) was reacted in dry DCM/DMF 9:1 mixture (2 mL) with O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (44.6 mg, 0.38 mmol), EDC.HCl (73 mg, 0.38 mmol), HOBt (51.5 mg, 0.38 mmol) and DIPEA (0.087 mL, 0.51 mmol) at r.t. for 4 h. The reaction was worked up with water, NH4Cl sat. sol., NaHCO3 sat. sol. and extracted with AcOEt. The organic layer was washed with brine dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was purified by silica gel flash chromatography eluting with DCM/MeOH 19/1 to provide 5-[2-(methylsulfanyl)pyrimidin-4-yl]-N-(tetrahydro-2H-pyran-2-yloxy)-1H-pyrazole-3-carboxamide 40 mg (48%) as a colorless oil.

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by silica gel flash chromatography
  7. washeluting with DCM/MeOH 19/1

Sources & evidence

ORD record
ord-7f1e4224b89b4d8eba9d7b26c3763ab2
Source dataset
uspto-grants-2016_03
Patent number
US09284298B2

Reaction notes

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