Diisopropylethylamine → HCID 68758071, compound

HRID 387584Notes

Reaction equation

HRID 387584 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[CH3:12][O:13][C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:21]=2[N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[NH:16][N:15]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:57]([O:61][C:62]([N:64]([CH:77]([CH3:79])[CH3:78])[CH2:65][C@H:66]([C:70]1[CH:75]=[CH:74][C:73]([Cl:76])=[CH:72][CH:71]=1)[C:67](O)=[O:68])=[O:63])([CH3:60])([CH3:59])[CH3:58]>C(Cl)Cl>[Cl:76][C:73]1[CH:74]=[CH:75][C:70]([C@H:66]([C:67]([N:26]2[CH2:25][CH2:24][N:23]([C:21]3[C:20]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:19][N:18]=[C:17]4[NH:16][N:15]=[C:14]([O:13][CH3:12])[C:22]=34)[CH2:28][CH2:27]2)=[O:68])[CH2:65][N:64]([CH:77]([CH3:78])[CH3:79])[C:62](=[O:63])[O:61][C:57]([CH3:59])([CH3:58])[CH3:60])=[CH:71][CH:72]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 68758794HCID 68758794, compound

Product 1

HCID 68758071HCID 68758071, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (0.0558 mL, 0.320 mmol) was added to 3-methoxy-5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.034 g, 0.080 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (0.0308 g, 0.0961 mmol) and (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0274 g, 0.080 mmol, see Example B) in DCM (1 mL) and stirred at room temperature for 1 hour. The reaction was concentrated to dryness. The resulting residue was dissolved in THF/MeOH (2 mL, 1:1), and an aqueous LiOH solution (1 mL, 2M) was added. It was stirred for 30 minutes, and then ether (20 mL) was added. The organic layer was separated, washed with brine (10 mL), and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(3-methoxy-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate as a solid. The solid was then dissolved in DCM (1 mL), and TFA (0.4 mL) was added. The mixture was stirred at room temperature for 2 hours and concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (S)-2-(4-chlorophenyl)-3-(isopropylamino)-1-(4-(3-methoxy-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propan-1-one dihydrochloride (0.029 g, 60%). MS APCI (+) m/z 533.3 detected.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. dissolutionThe resulting residue was dissolved in THF/MeOH (2 mL, 1:1)
  3. additionan aqueous LiOH solution (1 mL, 2M) was added
  4. stirringIt was stirred for 30 minutes
  5. additionether (20 mL) was added
  6. customThe organic layer was separated
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. customAfter removal of solvent
  10. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-32483f4d61fd4d63971bc9325f3fbf3f
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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