Trifluoroacetic acid → (S)-2-{3-[2-(6-Hydroxycarbamoyl-hexylcarbamoyl)-1H-indol-5-yl]-propionylamino}-3-phenyl-propionic acid cyclopentyl ester

HRID 548259Notes

Reaction equation

HRID 548259 reaction equation
[CH:1]1([O:6][C:7](=[O:49])[C@@H:8]([NH:16][C:17](=[O:48])[CH2:18][CH2:19][C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[NH:25][C:24]([C:29](=[O:47])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37](=[O:46])[NH:38][O:39]C2CCCCO2)=[CH:23]3)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(O)(C(F)(F)F)=O.C(Cl)Cl.CO>[CH:1]1([O:6][C:7](=[O:49])[C@@H:8]([NH:16][C:17](=[O:48])[CH2:18][CH2:19][C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[NH:25][C:24]([C:29](=[O:47])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37](=[O:46])[NH:38][OH:39])=[CH:23]3)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57971647(S)-3-Phenyl-2-(3-{2-[6-(tetrahydro-pyran-2-yloxycarbamoyl)-hexyl-carbamoyl]-1H-indol-5-yl}-propionylamino)-propionic acid cyclopentyl ester

Product 1

HCID 15940511(S)-2-{3-[2-(6-Hydroxycarbamoyl-hexylcarbamoyl)-1H-indol-5-yl]-propionylamino}-3-phenyl-propionic acid cyclopentyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 19108260TFA DCM MeOHSolvent

Procedure

(S)-3-Phenyl-2-(3-{2-[6-(tetrahydro-pyran-2-yloxycarbamoyl)-hexyl-carbamoyl]-1H-indol-5-yl}-propionylamino)-propionic acid cyclopentyl ester (200 mg. 0.297 mmol) was stirred at room temperature for 3.5 h in TFA/DCM/MeOH (1.5 ml/15 ml/15 ml). Further TFA (0.3 ml) was added and the reaction stirred for a further 30 minutes. The solution was concentrated in vacuo, resuspended in DCM and the solvent removed (×3). The crude material was purified by prep HPLC to give pure compound (100) (19.3 mg), LCMS purity 100%, m/z 591 [M++H]+, 1H NMR (400 MHz, MeOD), δ: 1.27-1.70 (16 H, m, alkyl), 1.97 (2H, t, CH2), 2.40 (2H, t, J=7.84 Hz, CH2), 2.76-2.85 (4H, m, 2×CH2), 3.25 (2H, t, J=7 Hz, CH2), 4.41 (1H, m, NHCHCO, 4.95 (1H, m, CH), 6.85 (1 H, s, CH), 6.95 (3H, m, Ar), 7.05 (3H, m, Ar), 7.20-7.26 (2H, s+d, J=8.5 Hz, Ar)

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customthe solvent removed (×3)
  3. customThe crude material was purified by prep HPLC

Sources & evidence

ORD record
ord-ca998d75c3db4c95a264dbe01c7a1062
Source dataset
uspto-grants-2011_05
Patent number
US07939666B2

Reaction notes

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