Potassium Carbonate → (2S)-1-{N-[2-(thiomorpholin-4-ylmethyl)hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrile

HRID 1015537Notes

Reaction equation

HRID 1015537 reaction equation
Cl.[N:2]1([CH2:8][C:9]23[CH2:17][CH:13]4[CH2:14][CH:15]([CH2:16]2)[C:11]([NH2:18])([CH2:12]4)[CH2:10]3)[CH2:7][CH2:6][S:5][CH2:4][CH2:3]1.Cl[CH2:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@H:24]1[C:28]#[N:29])=[O:22].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[N:2]1([CH2:8][C:9]23[CH2:17][CH:13]4[CH2:12][C:11]([NH:18][CH2:20][C:21]([N:23]5[CH2:27][CH2:26][CH2:25][C@H:24]5[C:28]#[N:29])=[O:22])([CH2:10]2)[CH:15]([CH2:14]4)[CH2:16]3)[CH2:7][CH2:6][S:5][CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11073883(2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrileHCID 866427431-(Thiomorpholin-4-ylmethyl) tricyclo[3.3.1.03,7]nonan-3-amine hydrochloride salt

Product 1

HCID 24853119(2S)-1-{N-[2-(thiomorpholin-4-ylmethyl)hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrileYield 35.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the hydrochloride salt (0.17 g, 0.51 mmol) obtained in step II above in DMSO (2.0 mL) at room temperature under nitrogen atmosphere was added (2S)-1-(chloroacetyl)pyrrolidine-2-carbonitrile (0.09 g, 0.52 mmol) and K2CO3 (0.35 g, 2.55 mmol. After stirring the reaction mixture for 3 h, it was diluted with EtOAc and washed with water and brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain (2S)-1-{N-[2-(thiomorpholin-4-ylmethyl)hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrile as an off-white solid (0.07 g) in 35% yield. m/z (M+1) 389; 1H NMR (CDCl3) 300 MHz δ 4.83-4.75 (m, 1H), 3.90-3.45 (m, 4H), 2.85-2.70 (m, 4H), 2.70-2.60 (m, 4H), 2.48-2.35 (m, 2H), 2.35-2.15 (m, 4H), 2.0-1.75 (m, 4H), 1.68-1.40 (m, 5H), 1.38-1.25 (m, 1H).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-8d028cab1d7c4ad1b9f4594a67f77f8c
Source dataset
uspto-grants-2011_07
Patent number
US07985759B2

Reaction notes

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