Diisopropylethylamine → HCID 68764699, compound

HRID 387592Notes

Reaction equation

HRID 387592 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[N:12]1([C:18]2[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][N:21]=[C:20]3[NH:28][N:29]=[CH:30][C:19]=23)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:53]([O:57][C:58]([N:60]([CH:73]([CH3:75])[CH3:74])[CH2:61][C@H:62]([C:66]1[CH:71]=[CH:70][C:69]([Cl:72])=[CH:68][CH:67]=1)[C:63](O)=[O:64])=[O:59])([CH3:56])([CH3:55])[CH3:54]>C(Cl)Cl>[Cl:72][C:69]1[CH:70]=[CH:71][C:66]([C@H:62]([C:63](=[O:64])[N:15]2[CH2:14][CH2:13][N:12]([C:18]3[C:23]([C:24]([F:26])([F:27])[F:25])=[CH:22][N:21]=[C:20]4[NH:28][N:29]=[CH:30][C:19]=34)[CH2:17][CH2:16]2)[CH2:61][N:60]([CH:73]([CH3:74])[CH3:75])[C:58](=[O:59])[O:57][C:53]([CH3:55])([CH3:54])[CH3:56])=[CH:67][CH:68]=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 68756410HCID 68756410, compound

Product 1

HCID 68764699HCID 68764699, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (0.0607 mL, 0.349 mmol) was added to a solution of 4-(piperazin-1-yl)-5-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.030 g, 0.0872 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (0.0336 g, 0.105 mmol) and (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0298 g, 0.0872 mmol, see Example B) in DCM (1 mL) and stirred at room temperature for 2 hours. The reaction was then 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. The solution 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 the solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-oxo-3-(4-(5-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propyl(isopropyl)carbamate as a solid. The solid was dissolved in DCM (1 mL), and TFA (0.4 mL) was added. The mixture was stirred at room temperature for 1 hour and then concentrated to dryness. The 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-(5-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propan-1-one dihydrochloride (0.027 g, 54%). MS APCI (+) m/z 495.3 detected.

Workup

  1. concentrationThe reaction was then 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. stirringThe solution 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 the solvent
  10. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3d13ae787df546a7a92257cd7be25e9b
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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