Hydrochloric Acid → N-[(5-bromo-2-methylphenyl)methyl]-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

HRID 564537Notes

Reaction equation

HRID 564537 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([CH2:8]NC(=O)OC(C)(C)C)[CH:7]=1.Cl.CC[N:21](CC)CC.[CH2:26]([N:28]1[C:32]2=[N:33][C:34]([CH2:57][CH3:58])=[C:35]([CH2:44][NH:45][C:46]([C:48]3[CH:49]=[C:50]([CH:54]=[CH:55][CH:56]=3)[C:51](O)=[O:52])=[O:47])[C:36]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:31]2[CH:30]=[N:29]1)[CH3:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([CH2:8][N:45]([CH2:44][C:35]2[C:36]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:31]3[CH:30]=[N:29][N:28]([CH2:26][CH3:27])[C:32]3=[N:33][C:34]=2[CH2:57][CH3:58])[C:46]([C:48]2[CH:56]=[CH:55][CH:54]=[C:50]([C:51]([NH2:21])=[O:52])[CH:49]=2)=[O:47])[CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578132773-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic AcidHCID 57813315tert-butyl N-[(5-bromo-2-methylphenyl)methyl]carbamate

Product 1

HCID 67006879N-[(5-bromo-2-methylphenyl)methyl]-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamideYield 107.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a clear solution of 1,1-dimethylethyl [(5-bromo-2-methylphenyl)methyl]carbamate (923 mg, 3.01 mmol) in DCM (10 mL) was added 4N HCl in dioxane (3 mL). Solid precipitated out from the solution after 30 min. The mixture was stirred at RT for another 1 h. It was then concentrated under vacuum to get rid of solvent. The resulting residue was re-dissolved in DCM. Et3N (1.5 mL, 10.3 mmol) was added followed by 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)-carbonyl]benzoic acid (1000 mg, 2.05 mmol) and HBTU (933 mg, 2.46 mmol). The mixture was stirred at RT overnight. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were then washed with water followed by the brine wash. The organic layer was then concentrated under vacuum to give a crude residue. It was then purified with CombiFlash chromatography, eluting with 0 to 10% methanol in DCM to obtain N-[(5-bromo-2-methylphenyl)methyl]-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide as a solid (1.4 g, 98%). LC-MS m/z 634 (M+H)+.

Workup

  1. customSolid precipitated out from the solution after 30 min
  2. concentrationIt was then concentrated under vacuum
  3. customto get rid of solvent
  4. stirringThe mixture was stirred at RT overnight
  5. customThe reaction was quenched with saturated NaHCO3
  6. extractionextracted with DCM twice
  7. washThe combined organic layers were then washed with water
  8. washwash
  9. concentrationThe organic layer was then concentrated under vacuum
  10. customto give a crude residue
  11. customIt was then purified with CombiFlash chromatography
  12. washeluting with 0 to 10% methanol in DCM

Sources & evidence

ORD record
ord-891021f2833b439285c747a1b02fc0ef
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

Loading…