Dimethylformamide → HCID 89692973, compound

HRID 1481879Notes

Reaction equation

HRID 1481879 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])[CH2:13][CH2:12]2)[C:8]([NH:24][C:25]([C:27]2[O:28][CH:29]=[CH:30][CH:31]=2)=[O:26])=[CH:7][C:3]=1[C:4](O)=[O:5].CN(C)C=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:70][N:71]([CH2:73][C:74]1[CH:75]=[C:76]([CH:79]=[CH:80][CH:81]=1)[CH2:77][NH2:78])[CH3:72]>O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([C:4](=[O:5])[NH:78][CH2:77][C:76]2[CH:79]=[CH:80][CH:81]=[C:74]([CH2:73][N:71]([CH3:72])[CH3:70])[CH:75]=2)=[CH:7][C:8]([NH:24][C:25]([C:27]2[O:28][CH:29]=[CH:30][CH:31]=2)=[O:26])=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])[CH2:13][CH2:12]2)[CH:10]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162280701-[3-(Aminomethyl)phenyl]-N,N-dimethylmethanamineHCID 89690467HCID 89690467, compound

Product 1

HCID 89692973HCID 89692973, compoundYield 19.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 40 ml scintillation vial equipped with a magnetic stir bar and fitted with a nitrogen inlet, the 2-chloro-5-[(furan-2-carbonyl)-amino]-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid 14b (135.70 mg, 0.31 mmol) was taken up in clean, dry N,N-dimethylformamide (4.00 ml, 51.66 mmol) and the mixture was stirred at room temperature under nitrogen until all solids were in solution. To this was added first the HATU (140.80 mg, 0.37 mmol) followed by the N,N-diisopropylethylamine (0.16 ml, 0.92 mmol) and the mixture was once again stirred until all solids were in solution. The 3-dimethylaminomethyl-benzylamine (76.00 mg, 0.46 mmol) was added and the reaction stirred at room temperature overnight. The reaction was diluted with 10 ml of water and 10 ml of ethyl acetate. The layers were separated and the product was extracted from the aqueous using ethyl acetate (3×15 ml). The organic phases were combined, washed with brine (1×25 ml) and saturated aqueous lithium chloride solution (2×25 ml). The product solution was dried over Na2SO4; the solution was then decanted and the solvent was removed under reduced pressure. The product was isolated using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. A secondary purification was required, using reverse-phase prep HPLC, eluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period. The product, furan-2-carboxylic acid [4-chloro-5-(3-dimethylaminomethyl-benzylcarbamoyl)-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 14c (37.30 mg, 0.06 mmol), was isolated as an off-white solid.

Workup

  1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
  2. customfitted with a nitrogen inlet
  3. stirringthe mixture was once again stirred until all solids
  4. stirringthe reaction stirred at room temperature overnight
  5. customThe layers were separated
  6. extractionthe product was extracted from the
  7. washwashed with brine (1×25 ml) and saturated aqueous lithium chloride solution (2×25 ml)
  8. dry with materialThe product solution was dried over Na2SO4
  9. customthe solution was then decanted
  10. customthe solvent was removed under reduced pressure
  11. customThe product was isolated
  12. washeluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane
  13. customA secondary purification
  14. washeluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period

Sources & evidence

ORD record
ord-3191f736f3cb432ea7d9378fcf2b8883
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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