1-Hydroxybenzotriazole → HCID 57756836, compound

HRID 228049Notes

Reaction equation

HRID 228049 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.Cl.CN(C)CCCN=C=NCC.Cl.[F:47][CH2:48][C@@H:49]([NH2:51])[CH3:50]>ClCCl.O.C(N(CC)CC)C>[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:51][C@@H:49]([CH3:50])[CH2:48][F:47])=[O:2])([CH2:11][CH2:10]2)[CH2:9][CH2:8]3)[C@H:17]([C:22]#[N:23])[CH2:18]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11851333(S)-1-Fluoro-2-propylamine HydrochlorideHCID 57634365(2S,4S)-1-[[N-(4-carboxybicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 57756836HCID 57756836, compoundYield 31.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

(2S,4S)-1-[[N-(4-Carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (100 mg) and 1-hydroxybenzotriazole (61.5 mg) were dissolved in dichloromethane (4 mL). While this solution was chilled in an ice bath, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (119 mg) was added and the mixture was stirred at room temperature for 1 hour. Subsequently, a mixture of (2S)-1-fluoro-2-propylamine hydrochloride (32.0 mg), triethylamine (56.0 μL) and dichloromethane (2 mL) was added and the resulting mixture was stirred at room temperature for further 8 hours. Following addition of water, the dichloromethane layer was collected. The dichloromethane layer washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by a silica gel column (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-4-fluoro-1-[[N-(4-[N-[(2S)-1-fluoro-2-propyl]amino]carbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (34.0 mg) as a white powder.

Workup

  1. temperatureWhile this solution was chilled in an ice bath
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature for further 8 hours
  4. customthe dichloromethane layer was collected
  5. washThe dichloromethane layer washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by a silica gel column (eluant:dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-3c3eacb47ef1415db3819b684e1bb8de
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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