Dimethylformamide → HCID 89692822, compound

HRID 1481873Notes

Reaction equation

HRID 1481873 reaction equation
[NH2:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][N:24]([C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=3[CH3:34])[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][CH2:15][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:73]1([C:76]2[O:77][CH:78]=[C:79]([C:81](O)=[O:82])[N:80]=2)[CH2:75][CH2:74]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][CH2:15][C:14]2=[O:18])=[CH:19][C:2]([NH:1][C:81]([C:79]2[N:80]=[C:76]([CH:73]3[CH2:75][CH2:74]3)[O:77][CH:78]=2)=[O:82])=[C:3]([N:21]2[CH2:22][CH2:23][N:24]([C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=3[CH3:34])[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 89692824HCID 89692824, compound

Product 1

HCID 89692822HCID 89692822, compoundYield 39.4%

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 5-amino-2-chloro-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-benzamide 12d (158.70 mg, 0.33 mmol) was taken up in clean, dry N,N-dimethylformamide (3.00 ml, 38.74 mmol) and the mixture was stirred at room temperature under an inert nitrogen atmosphere until all solids were taken up in solution. To this mixture was then added the HATU (188.20 mg, 0.49 mmol) followed by the N,N-diisopropylethylamine (0.17 ml, 0.98 mmol) and the mixture was again stirred until all solids were in solution. The 2-cyclopropyl-oxazole-4-carboxylic acid 1h (65.70 mg, 0.43 mmol) was then added to the reaction mixture and the reaction was allowed to stir under nitrogen at room temperature overnight. The reaction mixture was diluted with 15 ml of water and 15 ml of ethyl acetate. The layers were separated and the product was extracted from the aqueous solution using ethyl acetate (3×20 ml) and the organic phases were combined, washed with brine (1×25 ml) and saturated aqueous lithium chloride solution (2×25 ml). The solution was dried over Na2SO4; the product solution was decanted and the solvent was removed under reduced pressure. The resultant brown semi-solid was purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. The product, 2-cyclopropyl-oxazole-4-carboxylic acid {4-chloro-2-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-phenyl}-amide 12e (81.80 mg, 0.13 mmol), was isolated as an off-white solid and was submitted for testing.

Workup

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

Sources & evidence

ORD record
ord-a21f534e26c04a218f138bedccc42100
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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