Hydrochloric Acid → HCID 57813364, compound

HRID 564538Notes

Reaction equation

HRID 564538 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11](=[O:17])OC(C)(C)C)[CH:5]=[C:6]([F:8])[CH:7]=1.Cl.CCN(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(O)=O)=[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]=[C:4]([CH2:9][NH:10][C:11]([C:55]2[CH:54]=[CH:50][CH:49]=[C:48]([C:46]([NH:45][CH2:44][C:35]3[C:36]([NH:37][CH:38]4[CH2:39][CH2:40][O:41][CH2:42][CH2:43]4)=[C:31]4[CH:30]=[N:29][N:28]([CH2:26][CH3:27])[C:32]4=[N:33][C:34]=3[CH2:57][CH3:58])=[O:47])[CH:56]=2)=[O:17])[CH:5]=[C:6]([F:8])[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 57813285HCID 57813285, compound

Product 1

HCID 57813364HCID 57813364, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a clear solution of 1,1-dimethylethyl [(3-bromo-5-fluorophenyl)methyl]carbamate (280 mg, 1.11 mmol) 207310-29 in DCM (1 mL) was added 4N HCl in dioxane (1 mL). Solid precipitated out from the solution after 30 min. but the mixture was stirred at RT for another hour. It was then concentrated under vacuum to get rid of solvent. Then the residue was re-dissolved in DCM. Et3N (0.5 mL, 3.07 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 (300 mg, 0.62 mmol) and HBTU (311 mg, 3.07 mmol). The mixture was stirred at RT overnight. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The organic layer was then washed with water followed by the brine wash. The organic layer was then concentrated under vacuum to give a crude residue. It was purified with CombiFlash chromatography, eluting with 0 to 10% methanol in DCM to obtain N-[(3-bromo-5-fluorophenyl)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 (307 mg, 78%). LC-MS m/z 637 (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 organic layer was then washed with water
  8. washwash
  9. concentrationThe organic layer was then concentrated under vacuum
  10. customto give a crude residue
  11. customIt was purified with CombiFlash chromatography
  12. washeluting with 0 to 10% methanol in DCM

Sources & evidence

ORD record
ord-33b2b5c3137b465698843d392b60306c
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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