Water → HCID 67224085, compound

HRID 1963976Notes

Reaction equation

HRID 1963976 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.O.CCN(C(C)C)C(C)C.[Br:58][C:59]1[CH:68]=[CH:67][C:62]([C:63](=[N:65]O)[NH2:64])=[CH:61][CH:60]=1>CN(C)C=O>[Br:58][C:59]1[CH:68]=[CH:67][C:62]([C:63]2[N:65]=[C:10]([C@@H:9]3[CH2:13][CH2:14][CH2:15][N:8]3[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[O:12][N:64]=2)=[CH:61][CH:60]=1

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27568384-Bromo-N'-hydroxybenzene-1-carboximidamide

Product 1

HCID 67224085HCID 67224085, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-Boc-L-proline (2.5 g, 11.6 mmol) in N,N-dimethylformamide (18 mL), O-(Benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (TBTU, 3.73 g, 11.6 mmol), HOBt.H2O (0.36 g, 2.32 mmol) and DIPEA (10.2 ml, 58.1 mmol) were added. After the reaction mixture was stirred at room temperature for 5 minutes, 4-Bromo-N′-hydroxybenzimidamide 15 (2.5 g, 11.6 mmol) was added. The mixture was then stirred at 110° C. for 2.5 hours. After cooled to room temperature, the resulting mixture was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated to yield a crude yellow liquid, which was purified with chromatography (ethyl acetate: n-hexane=1:10) to give the desired product 16a (2.5 g).

Workup

  1. stirringThe mixture was then stirred at 110° C. for 2.5 hours
  2. temperatureAfter cooled to room temperature
  3. extractionthe resulting mixture was extracted with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a crude yellow liquid, which
  8. customwas purified with chromatography (ethyl acetate: n-hexane=1:10)

Sources & evidence

ORD record
ord-f8d418972cb8425887c7bd47c64c41f3
Source dataset
uspto-grants-2013_04
Patent number
US08415482B2

Reaction notes

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