Hydrochloric Acid → 4-{[5-(Azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide

HRID 1675664Notes

Reaction equation

HRID 1675664 reaction equation
[N:1]([CH2:4][C:5]1[C:6]([NH:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=[O:26])[CH2:21][CH2:20]2)=[C:7]2[CH:15]=[N:14][N:13]([CH2:16][CH3:17])[C:8]2=[N:9][C:10]=1[CH2:11][CH3:12])=[N+:2]=[N-:3].Cl.C([N:36](CC)C(C)C)(C)C.C[Si](N=C=O)(C)C>O1CCOCC1.ClCCl.O>[N:1]([CH2:4][C:5]1[C:6]([NH:18][CH:19]2[CH2:20][CH2:21][N:22]([C:25]([NH2:36])=[O:26])[CH2:23][CH2:24]2)=[C:7]2[CH:15]=[N:14][N:13]([CH2:16][CH3:17])[C:8]2=[N:9][C:10]=1[CH2:11][CH3:12])=[N+:2]=[N-:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 70696Trimethylsilyl isocyanate4×HCID 81531Diisopropylethylamine2×HCID 596832381,1-dimethylethyl 4-{[5-(azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxylate2×

Product 1

HCID 596832364-{[5-(Azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamideYield 28.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl 4-{[5-(azidomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxylate (8.9 g, 20.8 mmol, e.g. which can be as prepared in Intermediate 15) in 1,4-dioxane (50 ml) was treated with 4M HCl in 1,4-dioxane (125 ml). After 2 hours the solvent was evaporated and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic phase was collected and washed with saturated aqueous sodium bicarbonate solution. The combined aqueous phases were back-extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and the solvent was evaporated to give an oil (LCMS showed MH+=329; TRET=1.75 min). The oil was dissolved in dichloromethane (100 ml), and the solution was treated with N,N-diisopropylethylamine (6.1 ml, 35.0 mmol) followed by trimethylsilyl isocyanate (3.6 ml, 26.6 mmol, commercially available e.g. trimethylsilyl isocyanate 85% from Aldrich). The reaction mixture was stirred at room temperature overnight. Additional N,N-diisopropylethylamine (6.1 ml, 35.0 mmol) and trimethylsilyl isocyanate (3.6 ml, 26.6 mmol) was added. After stirring for a further 7 hours, additional trimethylsilyl isocyanate (3.6 ml) was added and stirring was continued over the weekend (e.g. this can be about 62 hours). Water (100 ml) was added and the mixture was stirred for 1 hour. The precipitated solid was collected by filtration, washed with water followed by diethyl ether, and then dried to give the title compound (2.21 g). LCMS m/z 372 [MH+]; TRET=2.08 min.

Workup

  1. customAfter 2 hours the solvent was evaporated
  2. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  3. customThe organic phase was collected
  4. washwashed with saturated aqueous sodium bicarbonate solution
  5. extractionThe combined aqueous phases were back-extracted with dichloromethane
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. customthe solvent was evaporated
  8. customto give an oil (LCMS showed MH+=329; TRET=1.75 min)
  9. stirringAfter stirring for a further 7 hours
  10. stirringstirring
  11. waitthis can be about 62 hours
  12. stirringthe mixture was stirred for 1 hour
  13. filtrationThe precipitated solid was collected by filtration
  14. washwashed with water
  15. customdried

Sources & evidence

ORD record
ord-b6f3fd63bdf8465c9e57215a9e459943
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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