1-Hydroxybenzotriazole → (2S,4S)-1-[(N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227939Notes

Reaction equation

HRID 227939 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:23][C:24]([N:26]1[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]1[C:32]#[N:33])=[O:25])[C:12]12[CH2:19][CH2:18][C:15]([C:20]([OH:22])=[O:21])([CH2:16][CH2:17]1)[CH2:14][CH2:13]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=[N:36]1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]([CH2:23][C:24]([N:26]1[CH2:30][C@@H:29]([F:31])[CH2:28][C@H:27]1[C:32]#[N:33])=[O:25])[C:12]12[CH2:19][CH2:18][C:15]([C:20]([O:22][N:35]3[C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=4[N:37]=[N:36]3)=[O:21])([CH2:14][CH2:13]1)[CH2:16][CH2:17]2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68842664(2S,4S)-1-[[N-Benzyloxycarbonyl-N-[4-carboxybicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 57756828(2S,4S)-1-[(N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrileYield 80.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S,4S)-1-[[N-Benzyloxycarbonyl-N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (91.5 mg) and 1-hydroxybenzotriazole (45.9 mg) were dissolved in N,N-dimethylformamide (2.0 mL). While the solution was chilled in an ice bath, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (95.9 mg) was added and the mixture was allowed to warm to room temperature and was stirred for 15 hours. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (eluant:ethyl acetate) to give (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (92.0 mg).

Workup

  1. temperatureWhile the solution was chilled in an ice bath
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by silica gel chromatography (eluant:ethyl acetate)

Sources & evidence

ORD record
ord-8e457e922b834e1a916deaa8c8027011
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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