Diisopropylethylamine → HCID 68735737, compound

HRID 387585Notes

Reaction equation

HRID 387585 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.ClC1C=CC([C@@H](CNC(C)C)[C:20]([N:22]2[CH2:27][CH2:26][N:25]([C:28]3[C:33]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][N:31]=[C:30]4[NH:40][N:41]=[C:42]([O:43][CH3:44])[C:29]=34)[CH2:24][CH2:23]2)=[O:21])=CC=1.[C:50]([O:54][C:55]([NH:57][C@H:58]([CH2:62][C:63]1[CH:68]=[CH:67][C:66]([Cl:69])=[CH:65][CH:64]=1)C(O)=O)=[O:56])([CH3:53])([CH3:52])[CH3:51].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:69][C:66]1[CH:65]=[CH:64][C:63]([CH2:62][C@@H:58]([NH:57][C:55](=[O:56])[O:54][C:50]([CH3:52])([CH3:51])[CH3:53])[C:20]([N:22]2[CH2:27][CH2:26][N:25]([C:28]3[C:33]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][N:31]=[C:30]4[NH:40][N:41]=[C:42]([O:43][CH3:44])[C:29]=34)[CH2:24][CH2:23]2)=[O:21])=[CH:68][CH:67]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 68758570HCID 68758570, compound

Product 1

HCID 68735737HCID 68735737, 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, see Example 9), (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.024 g, 0.080 mmol) and TBTU (0.0308 g, 0.0961 mmol) in DCM (1 mL) and stirred at room temperature for 1 hour. 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. It was stirred for 20 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 chromatography (hexane:ethyl acetate, 1:1) to give (R)-tert-butyl 3-(4-chlorophenyl)-1-(4-(3-methoxy-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate 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 2 hours and then 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 (R)-2-amino-3-(4-chlorophenyl)-1-(4-(3-methoxy-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)propan-1-one (0.036 g, 79%). MS APCI (+) m/z 491.3 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. stirringIt was stirred for 20 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 chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-8e3caab9d6ed44ba9e2b49fa815e05ad
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

Loading…