O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → HCID 178526864, compound

HRID 1639626Notes

Reaction equation

HRID 1639626 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([NH2:15])[C:11]([NH2:14])=[CH:12][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[N+:16]([C:19]1[C:20]([C:24](O)=O)=[N:21][NH:22][CH:23]=1)([O-:18])=[O:17].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]3[NH:14][C:24]([C:20]4[C:19]([N+:16]([O-:18])=[O:17])=[CH:23][NH:22][N:21]=4)=[N:15][C:10]=3[CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 251933094-(Morpholinomethyl)benzene-1,2-diamineHCID 178524956HCID 178524956, compound

Product 1

HCID 178526864HCID 178526864, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Morpholin-4-ylmethyl-benzene-1,2-diamine (1 mol. eq.) and 4-nitro-1H-pyrazole-3-carboxylic acid (1 mol. eq.) were dissolved in dimethylformamide (DMF) (10 vol.). O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) (1.2 mol. eq.) was added and the mixture was stirred at ambient temperature for 24 hours. The mixture was concentrated in vacuo until no further solvent was seen to distil. The residue was then dissolved in glacial acetic acid (10 vol.) and heated at 65° C. for ˜12 hours. The mixture was concentrated in vacuo and then dissolved in water (6 vol.) at 75° C. The black solution was cooled to 0-5° C. over 2 hours during which time a solid was formed. The solid was removed by filtration and the aqueous filtrate was diluted with ethyl acetate (4 vol.) and tetrahydrofuran (2 vol.). Solid NaHCO3 was added slowly to the stirred mixture until no further effervescence was observed and a pH of 6.8 was reached. The mixture was then stirred until a precipitation was observed. After standing the mixture at 0-5° C. for 2 hours, the solid was collected by filtration and washed with water (2 vol.) and ethyl acetate (2 vol.) and dried to give 5-morpholin-4-ylmethyl-2-(4-nitro-1H-pyrazol-3-yl)1H-benzimidazole as a brown solid (40%). (LC/MS (basic method): Rt 1.93, [M−H+]− 327).

Workup

  1. concentrationThe mixture was concentrated in vacuo until no further solvent
  2. customto distil
  3. dissolutionThe residue was then dissolved in glacial acetic acid (10 vol.)
  4. temperatureheated at 65° C. for ˜12 hours
  5. concentrationThe mixture was concentrated in vacuo
  6. dissolutiondissolved in water (6 vol.) at 75° C
  7. temperatureThe black solution was cooled to 0-5° C. over 2 hours during which time a solid
  8. customwas formed
  9. customThe solid was removed by filtration
  10. additionthe aqueous filtrate was diluted with ethyl acetate (4 vol.) and tetrahydrofuran (2 vol.)
  11. additionSolid NaHCO3 was added slowly to the stirred mixture until no further effervescence
  12. stirringThe mixture was then stirred until a precipitation
  13. customat 0-5° C.
  14. customfor 2 hours
  15. filtrationthe solid was collected by filtration
  16. washwashed with water (2 vol.) and ethyl acetate (2 vol.)
  17. customdried

Sources & evidence

ORD record
ord-f92d4adc13364b44a1e35a37e2ca2624
Source dataset
uspto-grants-2012_02
Patent number
US08110573B2

Reaction notes

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