Diisopropylethylamine → HCID 68759055, compound

HRID 387608Notes

Reaction equation

HRID 387608 reaction equation
Cl.Cl.[CH3:3][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[C:6]2[CH:12]=[N:11][NH:10][C:7]2=[N:8][CH:9]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:52]([O:56][C:57]([N:59]1[CH2:63][CH2:62][CH2:61][C@H:60]1[C@H:64]([C:68]1[CH:73]=[CH:72][C:71]([Cl:74])=[CH:70][CH:69]=1)[C:65](O)=[O:66])=[O:58])([CH3:55])([CH3:54])[CH3:53]>CN(C=O)C>[Cl:74][C:71]1[CH:70]=[CH:69][C:68]([C@@H:64]([C@@H:60]2[CH2:61][CH2:62][CH2:63][N:59]2[C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:58])[C:65]([N:16]2[CH2:15][CH2:14][N:13]([C:5]3[C:4]([CH3:3])=[CH:9][N:8]=[C:7]4[NH:10][N:11]=[CH:12][C:6]=34)[CH2:18][CH2:17]2)=[O:66])=[CH:73][CH:72]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564918(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acidHCID 68759696HCID 68759696, compound

Product 1

HCID 68759055HCID 68759055, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-methyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (75 mg, 0.194 mmol), diisopropylethylamine (135 μL, 0.775 mmol), HATU (73.7 mg, 0.194 mmol) and (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (79.0 mg, 0.233 mmol, see Example C) in DMF (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo. The resulting residue was redissolved in THF (5 mL) and treated with an aqueous solution of LiOH (2 mL, 0.5M) for 30 minutes. Next, the solvent was removed, and the resulting residue was suspended in EtOAc (50 mL) and washed with water (2×10 mL). The dried (MgSO4) organic phase was concentrated in vacuo, and the resulting residue was purified by reverse phase chromatography (Biotage, C-18 12M+) on Biotage SP4 unit using a gradient of 5-80% CH3CN/water to provide (S)-tert-butyl 2-((S)-1-(4-chlorophenyl)-2-(4-(5-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (70 mg, 0.130 mmol, 67.0% yield) as a solid after drying under high vacuum. LCMS (APCI+) m/z 539.2, 541.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe resulting residue was redissolved in THF (5 mL)
  3. additiontreated with an aqueous solution of LiOH (2 mL, 0.5M) for 30 minutes
  4. customNext, the solvent was removed
  5. washwashed with water (2×10 mL)
  6. dry with materialThe dried (MgSO4) organic phase
  7. concentrationwas concentrated in vacuo
  8. customthe resulting residue was purified by reverse phase chromatography (Biotage

Sources & evidence

ORD record
ord-89c2264ad2c64fea82043d566719ad23
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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