Ammonium Chloride → 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide

HRID 1877512Notes

Reaction equation

HRID 1877512 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.OC1C2N=NNC=2C=CC=1.[Cl-].[NH4+].C(N(C(C)C)CC)(C)C.[C:49]([C:51]1[N:56]=[CH:55][C:54]([C:57]2[C:69]3[C:68]4[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=4)[N:62]([C:70]4[CH:78]=[CH:77][C:73]([C:74](O)=[O:75])=[C:72]([NH:79][CH:80]5[CH2:85][CH2:84][O:83][CH2:82][CH2:81]5)[CH:71]=4)[C:61]=3[CH:60]=[CH:59][CH:58]=2)=[CH:53][CH:52]=1)#[N:50]>CN(C)C=O.O>[C:49]([C:51]1[N:56]=[CH:55][C:54]([C:57]2[C:69]3[C:68]4[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=4)[N:62]([C:70]4[CH:78]=[CH:77][C:73]([C:74]([NH2:8])=[O:75])=[C:72]([NH:79][CH:80]5[CH2:81][CH2:82][O:83][CH2:84][CH2:85]5)[CH:71]=4)[C:61]=3[CH:60]=[CH:59][CH:58]=2)=[CH:53][CH:52]=1)#[N:50]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 673081204-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 583383064-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamideYield 66.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

0.2 g of (1H-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP), 62 mg of hydroxybenzotriazole (HOBT), 33 mg of ammonium chloride and 0.25 ml of diisopropylethylamine are successively added to a solution of 0.15 g of 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzoic acid in 20 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 12 hours and then diluted with distilled water and extracted with ethyl acetate. The organic phase is subsequently washed with distilled water and a saturated solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by silica gel chromatography, elution being carried out with a mixture of cyclohexane and ethyl acetate (70/30 by volume), so as to give 100 mg of 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide in the form of a white solid, the characteristics of which are the following:

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase is subsequently washed with distilled water
  3. dry with materiala saturated solution of sodium chloride, dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by silica gel chromatography, elution
  7. additionbeing carried out with a mixture of cyclohexane and ethyl acetate (70/30 by volume)

Sources & evidence

ORD record
ord-91475fdb43064352907f4dcd7153a778
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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