Diisopropylethylamine → HCID 178518517, compound

HRID 624689Notes

Reaction equation

HRID 624689 reaction equation
[NH2:1][C:2]1[N:7]2[N:8]=[CH:9][C:10]([CH:11]=[C:12]3[NH:16][C:15](=[O:17])[NH:14][C:13]3=[O:18])=[C:6]2[N:5]=[C:4]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(OC([N:67]1[CH2:72][CH2:71][CH:70]([C:73](O)=[O:74])[CH2:69][CH2:68]1)=O)(C)(C)C>O.CN(C=O)C>[Cl:26][C:22]1[CH:21]=[C:20]([NH:19][C:4]2[CH:3]=[C:2]([NH:1][C:73]([CH:70]3[CH2:71][CH2:72][NH:67][CH2:68][CH2:69]3)=[O:74])[N:7]3[N:8]=[CH:9][C:10]([CH:11]=[C:12]4[C:13](=[O:18])[NH:14][C:15](=[O:17])[NH:16]4)=[C:6]3[N:5]=2)[CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178507871HCID 178507871, compound

Product 1

HCID 178518517HCID 178518517, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To the reaction vial, 5-((7-amino-5-(3-chlorophenylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)imidazolidine-2,4-dione (15 mg, 0.04 mmol) was added to DMF (0.2 mL) along with HBTU (30 mg, 0.08 mmol), DIEA (28 μL, 0.16 mmol) and 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (18 mg, 0.08 mmol). The reaction was stirred at room temperature for 8 hours then heated at 95° C. for 4 hours. The reaction was then cooled to room temperature and diluted with water. The solid was collected by filtration, washed with water, 1N HCl solution, and more water. The material was then dissolved in 5% DCM/MeOH and purified by prep HPLC. The isolated fractions were combined and evaporated to dryness. The material was dissolved in 1 mL of TFA/DCM (1:1) and stirred at room temperature for 1 hour. The solvent was removed by evaporation under a stream of nitrogen and the crude material was washed with 1N NaOH followed by water. The solid was collected by filtration and dried under vacuum overnight. The product, N-(5-(3-chlorophenylamino)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-4-carboxamide, was recovered as a solid in 2% yield. LCMS (M+1=481).

Workup

  1. temperaturethen heated at 95° C. for 4 hours
  2. temperatureThe reaction was then cooled to room temperature
  3. filtrationThe solid was collected by filtration
  4. washwashed with water, 1N HCl solution, and more water
  5. dissolutionThe material was then dissolved in 5% DCM/MeOH
  6. custompurified by prep HPLC
  7. customevaporated to dryness
  8. dissolutionThe material was dissolved in 1 mL of TFA/DCM (1:1)
  9. stirringstirred at room temperature for 1 hour
  10. customThe solvent was removed by evaporation under a stream of nitrogen
  11. washthe crude material was washed with 1N NaOH
  12. filtrationThe solid was collected by filtration
  13. customdried under vacuum overnight
  14. customThe product, N-(5-(3-chlorophenylamino)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-4-carboxamide, was recovered as a solid in 2% yield

Sources & evidence

ORD record
ord-9c3ee3ef7b1545c081f0556224204806
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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