Diisopropylethylamine → HCID 89692898, compound

HRID 1481885Notes

Reaction equation

HRID 1481885 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]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=3[CH3:24])[CH2:13][CH2:12]2)[C:8]([N+:25]([O-:27])=[O:26])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C([O:35]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:52]([N:55]([CH2:59][CH3:60])[CH:56]([CH3:58])C)([CH3:54])C.C1(C)C=CC=CC=1[N:67]1[CH2:72]CNCC1>O.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=3[CH3:24])[CH2:15][CH2:16]2)[C:8]([N+:25]([O-:27])=[O:26])=[CH:7][C:3]=1[C:4]([NH:67][CH2:72][CH2:60][CH2:59][N:55]1[CH2:52][CH2:54][CH2:58][C:56]1=[O:35])=[O:6]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 919652-MeppHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89690434HCID 89690434, compound

Product 1

HCID 89692898HCID 89692898, compoundYield 96.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

In a 40 ml scintillation vial equipped with a magnetic stir bar and fitted with a nitrogen inlet, the 2-chloro-4-[4-(5-fluoro-2-methyl-phenyl)-piperazin-1-yl]-5-nitro-benzoic acid 16e (110.60 mg, 0.28 mmol) was taken up in clean, dry dichloromethane (3.00 ml, 46.52 mmol) and was allowed to stir at room temperature under nitrogen until all solids were in solution. To this was then added the HATU (128.10 mg, 0.34 mmol) followed by the N,N-diisopropylethylamine (0.15 ml, 0.86 mmol) and again the mixture was stirred until all solids were dissolved. The 1-(3-amino-propyl)-pyrrolidin-2-one 1e (59.90 mg, 0.42 mmol) was added to the reaction and the mixture stirred at room temperature overnight. The reaction was diluted with 10 ml of water and 10 ml of dichloromethane. The layers were separated and the product was extracted from the aqueous using dichloromethane (3×15 ml). The organic phases were washed with brine (1×25 ml) and dried over MgSO4. The solution was then filtered under vacuum and the collected solution was concentrated under reduced pressure. The resultant orange oil was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. The product, 2-chloro-4-[4-(5-fluoro-2-methyl-phenyl)-piperazin-1-yl]-5-nitro-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 16f (140.10 mg, 0.27 mmol), was isolated as a yellow solid and was carried forward without further purification. LCMS (m/e)=518 (M+H).

Workup

  1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
  2. customfitted with a nitrogen inlet
  3. stirringagain the mixture was stirred until all solids
  4. dissolutionwere dissolved
  5. stirringthe mixture stirred at room temperature overnight
  6. customThe layers were separated
  7. extractionthe product was extracted from the
  8. washThe organic phases were washed with brine (1×25 ml)
  9. dry with materialdried over MgSO4
  10. filtrationThe solution was then filtered under vacuum
  11. concentrationthe collected solution was concentrated under reduced pressure
  12. customThe resultant orange oil was purified
  13. washeluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-f353d2b16537467192e02ffb85921442
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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