Dimethylformamide → (2S,4S)-4-fluoro-1-[[N-[4-[(2R)-N-(2-heptyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile

HRID 227977Notes

Reaction equation

HRID 227977 reaction equation
[C:1]([C:4]12[CH2:11][CH2:10][C:7]([NH:12][CH2:13][C:14]([N:16]3[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]3[C:22]#[N:23])=[O:15])([CH2:8][CH2:9]1)[CH2:6][CH2:5]2)(O)=[O:2].ON1C2C=CC=CC=2N=N1.CN(C)C=O.[NH2:39][C@@H:40]([CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH3:41]>ClCCl>[F:21][C@@H:19]1[CH2:20][N:16]([C:14](=[O:15])[CH2:13][NH:12][C:7]23[CH2:6][CH2:5][C:4]([C:1]([NH:39][C@@H:40]([CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH3:41])=[O:2])([CH2:9][CH2:8]2)[CH2:11][CH2:10]3)[C@H:17]([C:22]#[N:23])[CH2:18]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 6992808(2R)-heptan-2-amine2×HCID 57634365(2S,4S)-1-[[N-(4-carboxybicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 57756719(2S,4S)-4-fluoro-1-[[N-[4-[(2R)-N-(2-heptyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(2S,4S)-1-[[N-(4-Carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg), 1-hydroxybenzotriazole (23.7 mg), JANDAJEL-1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (289 mg) and N,N-dimethylformamide (1 mL) were mixed together and the mixture was stirred at room temperature for 3 hours. Subsequently, (2R)-2-aminoheptane (46.6 μL) was added and the mixture was stirred at room temperature for 17 hours and 40 minutes. This was followed by addition of dichloromethane (0.5 mL) and (2R)-2-aminoheptane (11.6 μL), stirring at room temperature for 4.5 hours, addition of JANDAJEL-1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (96.6 mg) and additional stirring at room temperature for 17 hours. Subsequently, (isocyanatomethyl)polystyrene (232 mg) was added and the mixture was stirred at room temperature for 2 hours. The insoluble material was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was then purified by silica gel column (eluant:ethyl acetate:methanol=10:1) to give (2S,4S)-4-fluoro-1-[[N-[4-[(2R)—N-(2-heptyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (9.0 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 17 hours and 40 minutes
  2. stirringstirring at room temperature for 4.5 hours
  3. stirringadditional stirring at room temperature for 17 hours
  4. stirringthe mixture was stirred at room temperature for 2 hours
  5. filtrationThe insoluble material was filtered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was then purified by silica gel column (eluant:ethyl acetate:methanol=10:1)

Sources & evidence

ORD record
ord-75f72e39eb264862b2e972be919e2506
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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