Ammonium Chloride → 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(3-hydroxypropyl)amino]benzamide

HRID 1877499Notes

Reaction equation

HRID 1877499 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][CH2:80][CH2:81][CH2:82][OH:83])[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][CH2:80][CH2:81][CH2:82][OH:83])[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 673090104-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(3-hydroxypropyl)amino]benzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 583381954-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(3-hydroxypropyl)amino]benzamideYield 33.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

260 mg of (1H-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP), 79 mg of hydroxybenzotriazole (HOBT), 41 mg (0.8 mmol) of ammonium chloride and 0.26 ml of diisopropylethylamine are successively added to a solution of 180 mg of 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(3-hydroxypropyl)amino]benzoic acid in 10 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 4 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 dichloromethane and methanol (96/4 by volume), and triturated in diisopropyl ether, so as to give 60 mg of 4-[4-(6-cyanopyridin-3-yl)-9H-carbazol-9-yl]-2-[(3-hydroxypropyl)amino]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 dichloromethane and methanol (96/4 by volume)
  8. customtriturated in diisopropyl ether

Sources & evidence

ORD record
ord-f5e57956051e4a428a85bf65c234063e
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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