Hydrochloric Acid → HCID 57813269, compound

HRID 564539Notes

Reaction equation

HRID 564539 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:16][NH:17][C:18](=[O:24])OC(C)(C)C)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=[O:15])[CH:9]=2)[CH:7]=1.Cl.CCN(CC)CC.[CH2:33]([N:35]1[C:39]2=[N:40][C:41]([CH2:64][CH3:65])=[C:42]([CH2:51][NH:52][C:53]([C:55]3[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=3)C(O)=O)=[O:54])[C:43]([NH:44][CH:45]3[CH2:50][CH2:49][O:48][CH2:47][CH2:46]3)=[C:38]2[CH:37]=[N:36]1)[CH3:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O1CCOCC1>[CH2:33]([N:35]1[C:39]2=[N:40][C:41]([CH2:64][CH3:65])=[C:42]([CH2:51][NH:52][C:53]([C:55]3[CH:63]=[CH:62][CH:61]=[C:57]([C:18]([NH:17][CH2:16][C:4]4[CH:5]=[C:6]([C:8]5[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=[O:15])[CH:9]=5)[CH:7]=[C:2]([F:1])[CH:3]=4)=[O:24])[CH:56]=3)=[O:54])[C:43]([NH:44][CH:45]3[CH2:46][CH2:47][O:48][CH2:49][CH2:50]3)=[C:38]2[CH:37]=[N:36]1)[CH3:34]

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 57813436HCID 57813436, compound

Product 1

HCID 57813269HCID 57813269, compoundYield 55.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a clear solution of 1,1-dimethylethyl [(5-fluoro-3′-formyl-3-biphenylyl)methyl]carbamate (486 mg, 1.48 mmol) in DCM (2 mL) was added 4N HCl in dioxane (1 mL). Solid precipitated out from the solution after 30 min but stirring was continued at RT for another 1 h. The mixture was then concentrated under vacuum to get rid of solvent. The resulting residue was re-dissolved in DCM. Et3N (1.14 mL, 8.20 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 (400 mg, 0.82 mmol) and HBTU (830 mg, 8.20 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 a brine wash. The organic layer was concentrated under vacuum to give a crude residue. It was purified with CombiFlash chromatography, eluting with 90% ethyl acetate in hexane to obtain N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(5-fluoro-3′-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (300 mg, 55%). LC-MS m/z 664 (M+H)+

Workup

  1. customSolid precipitated out from the solution after 30 min
  2. concentrationThe mixture 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 concentrated under vacuum
  10. customto give a crude residue
  11. customIt was purified with CombiFlash chromatography
  12. washeluting with 90% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c3430ea89539448ea0d880b23b49da90
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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