Uplc ms

A mixture of 2-chloro-5-(methylcarbamoyl)benzoic acid
(300 mg, 1.40 mmol) and 20 equiv of thionyl chloride (2.0 mL, 28 mmol)
was stirred at 80 °C for 2.5 h. The mixture was evaporated to
dryness and used immediately in the next step. A mixture of 2-(4-ethylphenyl)-1,3-benzoxazol-5-amine
(156 mg, 657 μmol), 1.05 equiv of 2-chloro-5-(methylcarbamoyl)benzoyl
chloride (160 mg, 689 μmol), and 3.0 equiv of TEA (270 μL,
2.0 mmol) in 4.0 mL of THF was stirred at r.t. for 12 h and evaporated
to dryness. The crude material was taken up in DCM, and the mixture
was stirred at r.t., filtered, and evaporated to dryness again to
give 150 mg (52% yield, 98% purity) of the title compound 9b.
UPLC-MS (Agilent, acidic conditions): t_R = 1.29 min. MS (ESI+): m/z = 434.1 [M + H]⁺.
¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.87 (s, 1 H), 8.82 (br d, J = 4.82
Hz, 1 H), 8.27 (d, J = 1.77 Hz, 1 H), 8.09–8.16
(m, 3 H), 7.99 (dd, J = 8.36, 2.28 Hz, 1 H), 7.75–7.80
(m, 1 H), 7.66–7.74 (m, 2 H), 7.47 (d, J =
8.36 Hz, 2 H), 2.79 (d, J = 4.56 Hz, 3 H), 2.72 (d, J = 7.60 Hz, 2 H), 1.23 (t, J = 7.60 Hz,
3 H).

A mixture of 2-(4-ethylphenyl)-1,3-benzoxazol-5-amine
(90.0 mg, 378 μmol), 1.3 equiv of 5-nitrothiophene-2-carboxylic
acid (85.0 mg, 491 μmol), 2 equiv of PyBrop (352 mg, 755 μmol),
and 5.0 equiv of DIPEA (330 μL, 1.9 mmol) in 3.1 mL of DMF was
stirred at r.t. until complete conversion. To the mixture were added
DCM and water, and the phases were separated. The aqueous phase was
extracted multiple times with DCM. The combined organic phases were
evaporated to dryness. Methanol was added to the remaining crude material,
and the solid material was filtered off to give 15 mg (10% yield,
100% purity) of the title compound 9g.
UPLC-MS
(Agilent, acidic conditions): t_R = 1.42
min. MS (ESI+): m/z = 394.1 [M +
H]⁺.
¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.81 (s, 1 H), 8.24 (d, J = 4.31
Hz, 1 H), 8.20 (d, J = 2.03 Hz, 1 H), 8.07–8.15
(m, 3 H), 7.80 (d, J = 8.87 Hz, 1 H), 7.69 (dd, J = 8.87, 2.03 Hz, 1 H), 7.47 (d, J = 8.36
Hz, 2 H), 2.72 (q, J = 7.60 Hz, 2 H), 1.24 (t, J = 7.60 Hz, 3 H.

A mixture of 2-(4-ethylphenyl)-1,3-benzoxazol-5-amine
(70.0 mg, 294 μmol), 1.2 equiv of 2-iodo-5-nitrobenzoic acid
(103 mg, 353 μmol), 2.4 equiv of DIPEA (120 μL, 710 μmol),
and 1.2 equiv of HATU (134 mg, 353 μmol) in 2.7 mL of DMF was
stirred at r.t. until complete conversion. The reaction mixture was
evaporated to dryness, and the remaining crude material was purified
by preparative HPLC (acidic conditions) to give 37 mg (24% yield,
100% purity) of the title compound 9k.
UPLC-MS
(Agilent, acidic conditions): t_R = 1.42
min. MS (ESI+): m/z = 514.0 [M +
H]⁺.
¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.81 (s, 1 H), 8.34 (d, J = 2.79
Hz, 1 H), 8.28 (d, J = 8.62 Hz, 1 H), 8.21 (d, J = 1.77 Hz, 1 H), 8.13 (d, J = 8.11 Hz,
2 H), 8.04 (dd, J = 8.62, 2.79 Hz, 1 H), 7.80 (d, J = 8.87 Hz, 1 H), 7.66 (dd, J = 8.87,
2.03 Hz, 1 H), 7.48 (d, J = 8.62 Hz, 2 H), 2.69–2.77
(m, 2 H), 1.24 (t, J = 7.60 Hz, 3 H).