Please cite this article in press as: Berdan et al., Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells, Cell Chem-
1H NMR (400MHz, CDCl3). d 7.23-7.16 (m, 4H), 6.27 (dd, J = 1.3, 17.0 Hz, 1H), 6.10 (s, 1H), 6.04 (dd, J = 10.3, 17.0 Hz, 1H), 5.60
(dd, J = 1.3, 10.3 Hz, 1H), 4.82-4.75 (m, 1H), 3.32 (dd, J = 7.1, 16.2 Hz, 2H), 2.84 (dd, J = 4.4, 16.1 Hz, 2H).
13C NMR (100MHz, CDCl3). d 165.4 ,140.9, 130.9, 126.8, 126.5, 124.9, 50.7, 40.1.
HRMS (+ESI). Calculated: 188.1070 (C12H14NO). Observed: 188.1068.
N-(7-(benzo[d][1,3]dioxol-5-yl)-2,3-dihydro-1H-inden-4-yl)acrylamide (TRH-1-78)
To a solution of N-(7-bromo-2,3-dihydro-1H-inden-4yl)acrylamide (TRH-1-65, 55 mg, 0.2 mmol) in a mixture of dioxane and water
(4:1 dioxane:water, 2.1 mL) under nitrogen atmosphere was added sequentially 3,4-(methylenedioxy)phenylboronic acid (70 mg,
0.4 mmol), potassium carbonate (74 mg, 0.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (24 mg, 10 mol%). The reaction
mixture was heated to a reflux and stirred overnight. The reaction was diluted with water (20 mL) and extracted with DCM
(3x20 mL). The combined organics were dried with magnesium sulfate, filtered, and evaporated, and the resulting crude was purified
by silica gel chromatography (0% to 25% ethyl acetate in hexanes) to give 7 mg of white solid (11% yield).
1H NMR (600 MHz, CDCl3). d 7.93 (d, J = 7.0 Hz, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.10 (s, 1H), 6.90 (s, 1H), 6.86 (t, J = 8.1 Hz, 2H), 6.45
(d, J = 16.8 Hz, 1H), 6.30 (dd, J = 10.3, 16.8 Hz, 1H), 5.79 (d, J = 10.2 Hz, 1H), 3.00 (t, J = 7.3 Hz, 2H), 2.88 (t, J = 7.3 Hz, 2H), 2.10 (quint,
7.3 Hz, 2H).
13C NMR (150 MHz, CDCl3). d 147.7, 146.7, 142.84, 142.81, 135.2, 134.9, 132.8, 131.3, 127.9, 127.8, 122.1, 119.8, 109.2, 108.3,
101.2, 36.8, 33.5, 30.5, 25.4.
HRMS (-ESI). Calculated: 306.1136 (C19H16NO3). Observed: 306.1130.
N-(3-oxo-2,3-dihydro-1H-inden-4-yl)acrylamide (TRH-1-129)
To a solution of 4-aminoindan (1.0 g, 7.5 mmol) in ethanol (20 mL) at 0ꢁC was added acetic anhydride (1.4 mL, 15.0 mmol). The so-
lution was raised to room temperature and stirred overnight, after which the solvent was evaporated. The residue was then dissolved
in acetone (50 mL) to which was added 15% aqueous magnesium sulfate (1.2 g in 6.75 mL of water) followed by potassium perman-
ganate (3.4 g, 17.0 mmol), and the resulting solution was stirred for 24 hours. The reaction filtered through a pad of celite, eluting with
chloroform and then water. The eluent was separated, and the aqueous layer was extracted several times with additional chloroform.
The combined organics were dried over magnesium sulfate, filtered and evaporated. The residue was then dissolved in a 6N HCl
solution (20 mL) and heated to 90ꢁC. After stirring for 5 hours, the solution was cooled, neutralized with small portions of potassium
carbonate, and extracted with ethyl acetate. The combined organics were dried with magnesium sulfate, filtered, and evaporated to
give 610 mg (55% over 3 steps) of crude 7-aminoindan-1-one which was used without further purification.
To a solution of 7-aminoindan-1-one in dichloromethane (15 mL) was added acryloyl chloride (0.39 mL, 4.8 mmol) followed by
triethylamine (0.67 mL, 4.8 mmol) at 0ꢁC under N2 atmosphere. The reaction mixture was allowed to warm to room temperature
and was stirred overnight. The solution was washed 1M HCl solution (2x) and brine, and the resulting crude was purified by silica
gel chromatography (10% to 20% ethyl acetate in hexanes) to yield 390 mg of white solid (47% yield, 26% combined over 4 steps).
1H NMR (400MHz, CDCl3). d 10.64 (s, 1H), 8.45 (d, J = 8.2 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.45 (dd, J = 1.0,
17.0 Hz, 1H), 6.33 (dd, J = 10.1, 17.0 Hz, 1H), 5.82 (dd, J = 1.0, 10.1 Hz, 1H), 3.11 (t, J = 11.5 Hz, 2H), 2.74-2.71 (m, 2H).
13C NMR (100MHz, CDCl3). d 209.3, 164.4, 155.9, 138.7, 137.0, 131.7, 128.0, 123.1, 120.8, 116.9, 36.5, 25.5.
HRMS (+ESI). Calculated: 202.0863 (C12H12NO2). Observed: 202.0860.
N-(3-hydroxy-2,3-dihydro-1H-inden-4-yl)acrylamide (TRH-1-133)
To a solution of N-(3-oxo-2,3-dihydro-1H-inden-4-yl)acrylamide (TRH-1-129, 201 mg, 1.0 mmol) in anhydrous methanol (7 mL) under
nitrogen atmosphere was added sodium borohydride (46.1 mg, 1.2 mmol). After 30 minutes of stirring, the reaction was quenched
with saturated sodium bicarbonate solution and extracted three times with DCM. The combined organics were dried with magnesium
Cell Chemical Biology 26, 1–9.e1–e22, July 18, 2019 e8