Dimethylformamide → HCID 71667531, compound

HRID 1481881Notes

Reaction equation

HRID 1481881 reaction equation
[NH2:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][N:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])[CH2:23][CH2:22]2)=[CH:4][C:5]([Cl:20])=[C:6]([CH:19]=1)[C:7]([NH:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:17][CH2:16][O:15][C:14]1=[O:18])=[O:8].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.[CH:72]1([C:75]2[O:76][CH:77]=[C:78]([C:80](O)=[O:81])[N:79]=2)[CH2:74][CH2:73]1>O.C(OCC)(=O)C>[Cl:20][C:5]1[C:6]([C:7](=[O:8])[NH:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][O:15][C:14]2=[O:18])=[CH:19][C:2]([NH:1][C:80]([C:78]2[N:79]=[C:75]([CH:72]3[CH2:74][CH2:73]3)[O:76][CH:77]=2)=[O:81])=[C:3]([N:21]2[CH2:22][CH2:23][N:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])[CH2:25][CH2:26]2)[CH:4]=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 252192732-Cyclopropyl-1,3-oxazole-4-carboxylic acidHCID 89692827HCID 89692827, compound

Product 1

HCID 71667531HCID 71667531, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 40 ml scintillation vial equipped with a magnetic stir bar, the 5-amino-2-chloro-N-[3-(2-oxo-oxazolidin-3-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide 15c (73.40 mg, 0.16 mmol) was taken up in clean, dry, reagent-grade N,N-dimethylformamide (3.00 ml, 38.74 mmol) and the reaction mixture was stirred under a nitrogen feed at room temperature until all solids were in solution. To this was then added the HATU (70.90 mg, 0.19 mmol) in one portion followed by the N,N-diisopropylethylamine (0.08 ml, 0.46 mmol) and the reaction mixture was stirred until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (35.70 mg, 0.23 mmol) was added the reaction was allowed to stir 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 (3×20 ml). The organic phases were combined, washed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml). The organic solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The product was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 7.5% MeOH in dichloromethane. The product required further purification and was thusly subjected to reverse-phase prep-HPLC, eluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period. The product, 2-cyclopropyl-oxazole-4-carboxylic acid [4-chloro-5-[3-(2-oxo-oxazolidin-3-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide 15d (26.60 mg, 0.04 mmol), was isolated as a white solid.

Workup

  1. customIn a 40 ml scintillation vial equipped with a magnetic stir bar
  2. customdry
  3. stirringto stir at room temperature overnight
  4. customThe layers were separated
  5. extractionthe product was extracted from the
  6. washwashed with brine (1×25 ml) and with saturated aqueous lithium chloride solution (2×25 ml)
  7. dry with materialThe organic solution was then dried over Na2SO4
  8. customthe solution was decanted
  9. customthe solvent was removed under reduced pressure
  10. customThe product was purified
  11. washeluting a gradient of 100% dichloromethane to 7.5% MeOH in dichloromethane
  12. custompurification
  13. washeluting a gradient of 30% MeOH in water to 100% MeOH over a 5 min period

Sources & evidence

ORD record
ord-796d6b8b04fb4f798515a948124351fb
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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