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

HRID 1015546Notes

Reaction equation

HRID 1015546 reaction equation
[O:1]=[S:2]1(=[O:23])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]23[CH2:21][CH:17]4[CH2:18][CH:19]([CH2:20]2)[C:15]([NH2:22])([CH2:16]4)[CH2:14]3)=[CH:9][CH:8]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:31][C:32]([N:34]1[CH2:38][CH2:37][CH2:36][C@H:35]1[C:39]#[N:40])=[O:33]>CS(C)=O.CCOC(C)=O>[O:1]=[S:2]1(=[O:23])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]23[CH2:21][CH:17]4[CH2:16][C:15]([NH:22][CH2:31][C:32]([N:34]5[CH2:38][CH2:37][CH2:36][C@H:35]5[C:39]#[N:40])=[O:33])([CH2:14]2)[CH:19]([CH2:18]4)[CH2:20]3)=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11073883(2S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrileHCID 670178591-[4-(1,1-Dioxidoisothiazolidin-2-yl) phenyl]tricyclo[3.3.1.03,7]nonan-3-amine

Product 1

HCID 24853219(2S)-1-{N-[2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrileYield 50%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 1-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]tricyclo[3.3.1.03,7]nonan-3-amine (0.4 g, 1.2 mmol) and K2CO3 (0.48 g, 3.6 mmol) in DMSO (4.8 mL) at ice bath temperature was added (2S)-1-(chloroacetyl)pyrrolidine-2-carbonitrile (0.25 g, 1.44 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 3 h. Upon completion of the reaction (checked 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-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrile as a white solid (0.28 g) in 50% yield. M.R, 214-216° C. m/z (M+1) 469; IR cm−1 3436, 2932, 2240, 1658, 1517, 1414, 1308, 1137, 952, 740. 1H NMR (300 MHz, CD3OD) δ: 7.35 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 4.85 (t, J=5.4 Hz, 1H), 4.15-3.95 (m, 2H), 3.81-3.70 (m, 3H), 3.60-3.50 (m, 1H), 3.42 (t, J=7.4 Hz, 2H), 2.65-2.45 (m, 4H), 2.40-1.75 (m, 14H).

Workup

  1. customUpon completion of the reaction (checked 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-5fb2d76f98204eddbb9907ca3ca55d25
Source dataset
uspto-grants-2011_07
Patent number
US07985759B2

Reaction notes

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