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

HRID 1015566Notes

Reaction equation

HRID 1015566 reaction equation
[O:1]=[S:2]1(=[O:17])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]12[CH2:15][CH:11]3[CH2:12][CH:13]([CH2:14]1)[C:9]([NH2:16])([CH2:10]3)[CH2:8]2.C([O-])([O-])=O.[K+].[K+].Cl[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C:33]#[N:34])=[O:27]>CS(C)=O.CCOC(C)=O>[O:1]=[S:2]1(=[O:17])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]12[CH2:15][CH:11]3[CH2:10][C:9]([NH:16][CH2:25][C:26]([N:28]4[CH2:32][CH2:31][CH2:30][C@H:29]4[C:33]#[N:34])=[O:27])([CH2:8]1)[CH:13]([CH2:12]3)[CH2:14]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11073883(2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrileHCID 593749741-(1,1-Dioxidoisothiazolidin-2-yl)tricyclo[3.3.1.03,7]nonan-3-amine

Product 1

HCID 24853440(2S)-1-{N-[2-(1,1-dioxidoisothiazolidin-2-yl) hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 1-(1,1-dioxidoisothiazolidin-2-yl)tricyclo[3.3.1.03,7]nonan-3-amine prepared as in preparation 10 (0.17 g, 0.66 mmol), and K2CO3 (0.28 g, 2.0 mmol) in DMSO (2.6 mL) at ice bath temperature was added (S)-1-(2-chloro-acetyl)pyrrolidine-2-carbonitrile (0.13 g, 0.66 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 3 h. Upon completion of the reaction (by TLC), the reaction mixture 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-(1,1-dioxidoisothiazolidin-2-yl) hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrile as a viscous liquid (0.1 g) in 40% yield. m/z (M+1) 393; 1H NMR (CDCl3) 300 MHz δ 4.80-4.75 (m, 1H), 3.70-3.37 (m, 4H), 3.36 (t, J=6.6 Hz, 2H), 3.16 (t, J=7.4 Hz, 2H), 2.43-2.37 (m, 1H), 2.35-2.13 (m, 9H), 2.05-1.99 (m, 1H), 1.95-1.75 (m, 5H), 1.70-1.63 (m, 1H), 1.54-1.47 (m, 1H).

Workup

  1. customUpon completion of the reaction (by TLC)
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-6714efdb098f428cbcf0b7f7a4ea2e05
Source dataset
uspto-grants-2011_07
Patent number
US07985759B2

Reaction notes

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