Water → HCID 86703325, compound

HRID 2410010Notes

Reaction equation

HRID 2410010 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25]([NH2:27])=O)[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:13]=[N:14][CH:15]=[N:16][CH:17]=3)[NH:9]2)=[CH:5][CH:4]=1.P(Cl)(Cl)(Cl)=O.C(=O)([O-])O.[Na+].O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23]([C:25]#[N:27])[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:17]=[N:16][CH:15]=[N:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 86703324HCID 86703324, compound

Product 1

HCID 86703325HCID 86703325, compoundYield 97.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 6-(6-methoxy-2-pyrimidin-5-yl-1H-indol-3-ylmethyl)pyridine-2-carboxamide (351 mg) in N,N-dimethylformamide (9.8 mL) was added phosphoryl chloride (0.133 mL) under ice-cooling, and the mixture was stirred under ice-cooling for 3 hours. To the reaction mixture were added a saturated aqueous sodium hydrogen carbonate and water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by aminopropylated silica gel column chromatography (eluting solvent: methanol-ethyl acetate) to obtain the title compound (326 mg). 1H-NMR (CDCl3) δ ppm: 3.87 (3H, s), 4.40 (2H, s), 6.81 (1H, dd, J=2.3, 8.5 Hz), 6.90-6.95 (1H, m), 7.30-7.39 (2H, m), 7.50-7.57 (1H, m), 7.64-7.72 (1H, m), 8.20 (1H, br s), 9.00 (2H, s), 9.20 (1H, s).

Workup

  1. temperaturecooling
  2. temperaturecooling for 3 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by aminopropylated silica gel column chromatography (eluting solvent: methanol-ethyl acetate)

Sources & evidence

ORD record
ord-29ce0eae33f547178b189446b928b131
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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