Trifluoroacetic acid → 3-(3-{1-[2-(2-Amino-propionylamino)-3-methyl-butyryl]-pyrrolidin-2-ylmethyl}-benzofuran-2-yl)-propionic acid ethyl ester

HRID 1054009Notes

Reaction equation

HRID 1054009 reaction equation
[CH2:1]([O:3][C:4](=[O:41])[CH2:5][CH2:6][C:7]1[O:8][C:9]2[CH:40]=[CH:39][CH:38]=[CH:37][C:10]=2[C:11]=1[CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:18](=[O:36])[CH:19]([NH:23][C:24](=[O:35])[CH:25]([NH:27]C(OC(C)(C)C)=O)[CH3:26])[CH:20]([CH3:22])[CH3:21])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:41])[CH2:5][CH2:6][C:7]1[O:8][C:9]2[CH:40]=[CH:39][CH:38]=[CH:37][C:10]=2[C:11]=1[CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:18](=[O:36])[CH:19]([NH:23][C:24](=[O:35])[CH:25]([NH2:27])[CH3:26])[CH:20]([CH3:22])[CH3:21])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 671489463-(3-{1-[2-(2-tert-Butoxycarbonylamino-propionylamino)-3-methyl-butyryl]-pyrrolidin-2-ylmethyl}-benzofuran-2-yl)-propionic acid ethyl ester

Product 1

HCID 671483093-(3-{1-[2-(2-Amino-propionylamino)-3-methyl-butyryl]-pyrrolidin-2-ylmethyl}-benzofuran-2-yl)-propionic acid ethyl esterYield 42.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 51 (160 mg, 0.28 mmol) in DCM (10 mL) was added TFA (2 mL) at ambient temperature. After 2.5 h, the solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. A portion (˜50%) of the crude material was purified by reverse-phase HPLC (C18, 10-100% ACN/water containing 0.1% HOAc) to afford 56 mg of 52 as a white solid. 1H NMR (DMSO, 300 MHz) 58.03 (d, J=8.7 Hz, 1H), 7.77 (m, 1H), 7.43-7.41 (m, 1H), 7.21 (m, 2H), 4.37 (app t, J=8.1 Hz, 1H), 4.19 (m, 1H), 4.01 (q, J=7.2 Hz, 2H), 3.65 (m, 1H), 3.56 (app d, J=6.6 Hz, 1H), 3.28 (m, 1H), 3.06-3.01 (m, 3H), 2.68 (app t, J=7.2 Hz, 2H), 2.07-1.96 (m, 1H), 1.63 (m, 1H), 1.54 (m, 1H), 1.13-1.09 (m, 6H), 0.90 (d, J=6.3 Hz, 3H), 0.85 (d, J=6.3 Hz, 3H) ppm. Mass spectrum: m/z 472 [M+H]+; and, 494 [M+Na]+.

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with aqueous NaHCO3, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customA portion (˜50%) of the crude material was purified by reverse-phase HPLC (C18, 10-100% ACN/water containing 0.1% HOAc)

Sources & evidence

ORD record
ord-267a2612e705434d83eb040641460e82
Source dataset
uspto-grants-2016_07
Patent number
US09394249B2

Reaction notes

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