Triethylamine → 2-(4-but-2-ynyloxy-benzenesulfonylamino)-3-(1-cyclobutylmethyl-1H-indol-3-yl)-propionic acid

HRID 2104211Notes

Reaction equation

HRID 2104211 reaction equation
C(N(CC)CC)C.[CH:8]1([CH2:12][N:13]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:15]([CH2:16][C@H:17]([C:19]([OH:21])=[O:20])[NH2:18])=[CH:14]2)[CH2:11][CH2:10][CH2:9]1.[CH2:28]([O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1)[C:29]#[C:30][CH3:31]>O.O1CCOCC1>[CH2:28]([O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39]([NH:18][CH:17]([CH2:16][C:15]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:13]([CH2:12][CH:8]3[CH2:11][CH2:10][CH2:9]3)[CH:14]=2)[C:19]([OH:21])=[O:20])(=[O:41])=[O:40])=[CH:35][CH:34]=1)[C:29]#[C:30][CH3:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 111959284-But-2-ynyloxy-benzenesulfonyl chlorideHCID 578059941-cyclobutylmethyl-D-tryptophan

Product 1

HCID 566573002-(4-but-2-ynyloxy-benzenesulfonylamino)-3-(1-cyclobutylmethyl-1H-indol-3-yl)-propionic acid

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Triethylamine (0.275 mL, 1.97 mmol) was added to a solution of crude 1-cyclobutylmethyl-D-tryptophan of Step 2 (0.657 mmol) and 4-but-2-ynyloxy-benzenesulfonyl chloride (0.177 g, 0.723 mmol) in H2O-dioxane (2 mL:3 mL) at room temperature. The reaction mixture was stirred for 20 hours at room temperature. The mixture was then concentrated and acidified with HCl. The mixture was extracted with ethyl acetate (3×10 mL). The organic solution was washed with H2O and brine, dried over Na2SO4, and concentrated. The residue was purified by RP-HPLC to give 0.152 g (48% in 3 steps) of the title compound as a yellow solid. 1H NMR (DMSO-d6): 400 MHz δ 12.57 (bs, 1H), 8.07 (d, J=8.4 Hz, 1H), 7.49 (d, J=7.2 Hz, 2H), 7.37 (d, J=8.0 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.08 (t, J=7.4 Hz, 1H), 7.02 (s, 1H), 6.96-6.88 (m, 3H), 4.77 (q, J=2.4 Hz, 2H), 4.04 (d, J=6.8 Hz, 2H), 3.84 (q, J=6.8 Hz, 1H), 3.02 (dd J=14.4, 6.4 Hz, 1H), 2.82 (dd J=14.4, 8.4 Hz, 1H), 2.67 (p, J=7.6 Hz, 1H), 1.91 (m, 2H), 1.83 (m, 5H), 1.75 (m, 2H); HRMS: calcd for C26H29N2O5S (ESI+, [M+H]1+), 481.1792; found 481.1786; LCMS m/z (ESI) [M+H] 481, retention time=3.22 min.

Workup

  1. concentrationThe mixture was then concentrated
  2. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  3. washThe organic solution was washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-e0244e6391764517ad6294cc9d6c2b61
Source dataset
uspto-grants-2009_08
Patent number
US07576222B2

Reaction notes

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