Dimethylformamide → Bisegliptin

HRID 606726Notes

Reaction equation

HRID 606726 reaction equation
Br.[NH2:2][C:3]12[CH2:10][CH2:9][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH2:7][CH2:8]1)[CH2:5][CH2:4]2.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[F:27][C@@H:28]1[CH2:32][N:31]([C:33](=[O:45])[CH2:34]OS(C2C=CC=CC=2)(=O)=O)[C@H:30]([C:46]#[N:47])[CH2:29]1>O>[CH2:14]([O:13][C:11]([C:6]12[CH2:5][CH2:4][C:3]([NH:2][CH2:34][C:33]([N:31]3[CH2:32][C@@H:28]([F:27])[CH2:29][C@H:30]3[C:46]#[N:47])=[O:45])([CH2:10][CH2:9]1)[CH2:8][CH2:7]2)=[O:12])[CH3:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 24781881(2S,4S)-1-[2-(benzenesulfonyloxy)acetyl]-4-fluoropyrrolidine-2-carbonitrileHCID 67053432Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrobromide

Product 1

HCID 11688894BisegliptinYield 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrobromide (612 mg), potassium carbonate (608 mg) and N,N-dimethylformamide (4 mL) were mixed together. To this mixture, (2S,4S)-4-fluoro-1-[2-(benzenesulfonyloxy)acetyl]pyrrolidine-2-carbonitrile (625 mg) was added at 40° C. and the mixture was further stirred for 1 hour. Subsequently, water (10 mL) was added and the resulting crystal was collected by filtration. This product was washed with water (5 mL) and dried at 50° C. under reduced pressure to give (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]ac etyl]-4-fluoropyrrolidine-2-carbonitrile as a colorless powder (581 mg, 83% yield). This compound was identical to the compound obtained in Example 7.

Workup

  1. filtrationthe resulting crystal was collected by filtration
  2. washThis product was washed with water (5 mL)
  3. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-80028d8024e1440faf5b2a5996d4929a
Source dataset
uspto-grants-2011_03
Patent number
US07915427B2

Reaction notes

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