1,2-Dichloroethane → HCID 46893990, compound

HRID 656668Notes

Reaction equation

HRID 656668 reaction equation
[C:1]([C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([C@H:10]1[NH:14][C:13](=[O:15])[C@H:12]([CH2:16][C:17]([OH:19])=O)[CH2:11]1)=[O:9])#[N:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH2:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:36][NH:35]1>O1CCOCC1.C(Cl)Cl>[CH2:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:36][N:35]1[C:17](=[O:19])[CH2:16][C@H:12]1[C:13](=[O:15])[NH:14][C@H:10]([C:8]([N:4]2[CH2:5][CH2:6][CH2:7][C@H:3]2[C:1]#[N:2])=[O:9])[CH2:11]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 422478IsoindolineHCID 59487306HCID 59487306, compound

Product 1

HCID 46893990HCID 46893990, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of [(3S,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}-2-oxopyrrolidin-3-yl]acetic acid (265 mg, 0.50 mmol) and HOBt (42 mg, 0.55 mmol) in 1,4-dioxane (3 mL) was added a solution of EDC (105 mg, 0.55 mmol) in CH2Cl2 (3 mL). The mixture was stirred for 10 min at room temperature. Isoindoline (65 mg, 0.55 mmol) in CH2Cl2 (2 mL) was added with stirring. After 16 h, the reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), 1 N aqueous citric acid (10 mL), and brine (10 mL). The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified over silica gel using CH2Cl2/MeOH (98:2) as an eluent to yield compound 1 (128 mg, 0.35 mmol, 70%). 1H NMR (300 MHz, CDCl3): (6/1 mixture of trans/cis amide rotomers) δ 7.30-7.26 (m, 4H), 6.56 (s, 0.86H), 6.06 (s, 0.14H), 4.82-4.77 (m, 4.86H, overlapped two singlet at 4.82, 4.77), 4.60 (d, J=6.6 Hz, 0.14H), 4.55 (d, J=9.0 Hz, 0.14H), 4.40 (dd, J=3.0, 9.0 Hz, 0.86H), 3.61-3.04 (m, 2H), 3.02-2.88 (m, 2H), 2.68-2.36 (m, 3H), 2.29-2.12 (m, 4H). MS (ES+) m/z calcd. for C20H22N4O3: 366.17. found: 367.1 (M+H).

Workup

  1. stirringwith stirring
  2. waitAfter 16 h
  3. washthe reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), 1 N aqueous citric acid (10 mL), and brine (10 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified over silica gel

Sources & evidence

ORD record
ord-20c1c7b034ac450a9ef3167c0f1b795a
Source dataset
uspto-grants-2011_12
Patent number
US08071787B2

Reaction notes

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