Diisopropylethylamine → HCID 58338182, compound

HRID 1877450Notes

Reaction equation

HRID 1877450 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([C:23](O)=O)[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)=[N:8][CH:9]=1)(=[O:3])[NH2:2].[CH:26]1[C:31]([F:32])=[CH:30][C:29]([NH2:33])=[C:28]([NH2:34])[CH:27]=1.F[B-](F)(F)F.C(OC(C(=NOC(N(C)C)=[N+](C)C)C#N)=O)C.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(O)(=O)C.O>[F:32][C:31]1[CH:26]=[CH:27][C:28]2[N:34]=[C:23]([C:18]3[C:17]4[C:16]5[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=5)[N:10]([C:7]5[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[CH:9][N:8]=5)[C:22]=4[CH:21]=[CH:20][CH:19]=3)[NH:33][C:29]=2[CH:30]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 1645844-Fluorobenzene-1,2-diamineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67307516HCID 67307516, compound

Product 1

HCID 58338182HCID 58338182, compoundYield 41.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a 50 ml round-bottomed flask, a mixture of 210 mg of 9-(5-carbamoylpyridin-2-yl)-9H-carbazole-4-carboxylic acid, obtained according to the preceding stage, 105 mg of 4-fluoro-O-phenylenediamine, 273 mg of O-((ethoxycarbonyl)cyanomethyleneamino)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TOTU) and 138 μl of diisopropylethylamine in 36 ml of dimethylformamide is stirred at ambient temperature for 12 hours. 300 ml of water are added to the reaction medium and then the aqueous phase is extracted with twice 300 ml of ethyl acetate. The organic phases are combined, washed with 100 ml of a saturated solution of sodium chloride, dried over magnesium sulphate and then evaporated to dryness under vacuum. The crude residue obtained is dissolved with 8.5 ml of glacial acetic acid in a 20 ml tube reactor and heated in a microwave at 110° C. for 1 hour. After return to ambient temperature, the reaction mixture is concentrated under reduced pressure and then 10 ml of water and a 10% aqueous solution of sodium hydrogen carbonate are added in order to bring the pH to around 8. The aqueous phase is extracted with 1×100 ml of ethyl acetate and then the organic phase is concentrated under reduced pressure. The crude residue obtained is purified by silica gel chromatography (15-40 μm), elution being carried out with a mixture of dichloromethane and 7N ammonia in methanol (95/5 by volume). 110 mg of 6-[4-(6-fluoro-1H-benzimidazol-2-yl)-9H-carbazol-9-yl]nicotinamide are thus obtained in the form of an off-beige solid, the characteristics of which are the following:

Workup

  1. customobtained
  2. extractionthe aqueous phase is extracted with twice 300 ml of ethyl acetate
  3. washwashed with 100 ml of a saturated solution of sodium chloride
  4. dry with materialdried over magnesium sulphate
  5. customevaporated to dryness under vacuum
  6. customThe crude residue obtained
  7. temperatureheated in a microwave at 110° C. for 1 hour
  8. concentrationAfter return to ambient temperature, the reaction mixture is concentrated under reduced pressure
  9. addition10 ml of water and a 10% aqueous solution of sodium hydrogen carbonate are added in order
  10. extractionThe aqueous phase is extracted with 1×100 ml of ethyl acetate
  11. concentrationthe organic phase is concentrated under reduced pressure
  12. customThe crude residue obtained
  13. customis purified by silica gel chromatography (15-40 μm), elution
  14. additionbeing carried out with a mixture of dichloromethane and 7N ammonia in methanol (95/5 by volume)

Sources & evidence

ORD record
ord-710bac4a284a46b69245ffae5e3139f7
Source dataset
uspto-grants-2012_11
Patent number
US08309721B2

Reaction notes

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