Triethylamine → (S)-1-[2-(2-benzenesulfonyl-ethyl-BOC-amino)-acetyl]-pyrrolidine-2-carbonitrile

HRID 1869647Notes

Reaction equation

HRID 1869647 reaction equation
[C:1]1([S:7]([CH2:10][CH2:11][N:12]([CH2:20][C:21](O)=[O:22])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]#[N:30].CCN=C=NCCCN(C)C.C(N(CC)CC)C>C(Cl)Cl>[C:1]1([S:7]([CH2:10][CH2:11][N:12]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:20][C:21]([N:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[C:29]#[N:30])=[O:22])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 5706552(2S)-pyrrolidine-2-carbonitrileHCID 69034616[(2-benzenesulfonyl-ethyl)-BOC-amino]-acetic acid

Product 1

HCID 69033930(S)-1-[2-(2-benzenesulfonyl-ethyl-BOC-amino)-acetyl]-pyrrolidine-2-carbonitrileYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[(2-benzenesulfonyl-ethyl)-BOC-amino]-acetic acid (288 mg, 0.84 mmol) and (S)-pyrrolidine-2-carbonitrile (111 mg, 0.84 mmol) were combined in CH2Cl2 (10 mL) at 0° C. EDCI (192 mg, 1.0 mmol) and triethylamine (280 μL, 2.0 mmol) were added, and the reaction stirred for 3 h while warming to r.t. The solution was washed with 0.1 N HCl and brine, dried (Na2SO4), and concentrated in vacuo. Purification by silica gel chromatography (75% EtOAc/hexanes) gave 188 mg (53%) of (S)-1-[2-(2-benzenesulfonyl-ethyl-BOC-amino)-acetyl]-pyrrolidine-2-carbonitrile as a white foam. 1H NMR (300 MHz, CDCl3): δ 7.91 (t, 2H, J=4.8 Hz), 7.54-7.69 (m, 3H), 4.69-4.79 (m, 1H), 4.17 (t, 1H, J=12.0 Hz), 3.87 (t, 1H, J=12.0 Hz), 3.40-3.77 (m, 6H), 2.12-2.32 (m, 4H), 1.39 (d, 9H, J=5.1 Hz). MS (ES) [m+H]/z calculated for C20H27N3O5S+H 422.17, found 422.10.

Workup

  1. washThe solution was washed with 0.1 N HCl and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customPurification by silica gel chromatography (75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a6e3bd49cb35406c8ccd394af7584564
Source dataset
uspto-grants-2009_12
Patent number
US07638638B2

Reaction notes

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