ACCEPTED MANUSCRIPT
4.1.3.6. 5-((3,3-Difluoroazetidin-1-yl)sulfonyl)-
Yield 79%. 1H NMR (400 MHz, DMSO-d6
10.92 (s, 1H), 8.21 (dd,
1H), 7.73 (t, = 9.2 Hz, 1H), 7.52 – 7.42 (m, 2H), 4.36 (t,
= 12.7 Hz, 4H). 13C NMR (101 MHz, DMSO-d6
Hz), 161.6, 149.4 (dd, = 243.8, 13.2 Hz), 146.3 (dd, = 242.7, 12.6 Hz), 135.9 (dd,
(d, = 4.4 Hz), 130.4 (d,
6.0, 3.4 Hz), 114.8, 112.1, 109.5 (d,
N
-(3,4-difluorophenyl)-2-fluorobenzamide (4f)
= 6.3, 2.5 Hz, 1H), 8.20 – 8.11 (m, 1H), 7.93 – 7.86 (m,
162.4 (d, = 258.7
= 10.2 Hz), 131.3
= 17.8 Hz), 117.5, 116.9 (dd,
-98.3, -105.8, -
)
δ
J
J
J
)
δ
J
J
J
J
= 9.1, 2.9 Hz), 133.6 (d, J
J
J
= 3.2 Hz), 126.1 (d,
J
= 16.5 Hz), 118.6 (d,
J
= 23.7 Hz), 118.1 (d,
J
J =
J
= 21.5 Hz), 62.4 (t,
J
= 27.6 Hz), 46.1. 19F NMR (377 MHz, DMSO-d6
)
δ
136.9 (d,
J
= 22.8 Hz), -143.5 (d, J
= 23.1 Hz). HRMS (ESI): m/z [M+H]+ calcd for C16H11F5N2O3S: 407.0489, found: 407.0484.
4.1.3.7.
N-(3,4-Difluorophenyl)-2-fluoro-5-((2-oxopyrrolidin-1-yl)sulfonyl)benzamide (4g)
Note: 2-pyrolidinone (24 mg, 0.286 mmol) was treated with sodium hydride (12 mg, 0.286 mmol, 60% dispersion in mineral oil) in
THF (3 mL) prior to the addition of 3. Yield 37%. 1H NMR (400 MHz, Acetone-d6
9.93 (s, 1H), 8.41 (dd, = 6.5, 2.5 Hz, 1H),
8.30 – 8.20 (m, 1H), 8.03 – 7.92 (m, 1H), 7.57 (dd, = 10.0, 8.8 Hz, 1H), 7.55 – 7.49 (m, 1H), 7.36 (dt, = 10.5, 9.0 Hz, 1H), 4.01
(t, = 7.0 Hz, 2H), 2.46 (dd,
= 8.4, 7.6 Hz, 2H), 2.20 – 2.11 (m, 2H). 13C NMR (101 MHz, Acetone-d6 13C NMR (101 MHz,
Acetone-d6 173.5, 162.5 (d, = 258.3 Hz), 160.9, 149.6 (dd, = 244.3, 13.3 Hz), 146.6 (dd, = 243.4, 12.9 Hz), 135.5 (dd,
8.9, 3.2 Hz), 135.2, 133.3 (d, = 10.6 Hz), 130.8 (d, = 4.4 Hz), 124.7 (d, = 16.2 Hz), 117.5 (d, = 5.5 Hz), 117.2, 116.6 – 115.9
(m), 109.4 (d, -107.9, -139.5 – -139.7 (m), -146.0 – -146.2 (m).
= 22.2 Hz), 47.4, 31.6, 18.1. 19F NMR (377 MHz, Acetone-d6
HRMS (ESI): m/z [M+H]+ calcd for C17H13F3N2O4S: 399.0626, found: 399.0619.
)
δ
J
J
J
J
J
) δ
)
δ
J
J
J
J =
J
J
J
J
J
) δ
4.1.3.8. 5-(
Yield 77%. 1H NMR (400 MHz, DMSO-d6
Hz, 1H), 7.48 – 7.42 (m, 2H), 2.21 – 2.08 (m, 1H), 0.58 – 0.47 (m, 2H), 0.45 – 0.36 (m, 2H). 13C NMR (101 MHz, DMSO-d6
N
-Cyclopropylsulfamoyl)-
N
-(3,4-difluorophenyl)-2-fluorobenzamide (4h)
)
δ
10.86 (s, 1H), 8.09 (s, 2H), 8.07 – 7.98 (m, 1H), 7.91 – 7.84 (m, 1H), 7.65 (t, J = 9.2
)
δ
162.0, 161.2 (d,
6.1 Hz), 132.0 (d,
109.5 (d,
= 21.7 Hz), 24.6, 5.6. 19F NMR (377 MHz, DMSO-d6
(ESI): m/z [M+H]+ calcd for C16H13F3N2O3S: 371.0677, found: 371.0672.
J
= 256.1 Hz), 149.4 (dd,
J
= 243.7, 13.2 Hz), 146.3 (dd,
= 16.7 Hz), 118.2, 118.0 (d,
-108.2, -136.9 (d,
J
= 242.7, 12.9 Hz), 137.3 (d,
J
= 3.2 Hz), 135.9 (d,
J
=
J
= 9.9 Hz), 129.4 (d, = 4.0 Hz), 125.6 (d,
J
J
J
= 4.6 Hz), 116.8 (dd, J = 5.7, 3.4 Hz),
J
)
δ
J
= 23.0 Hz), -143.5 (d,
J
= 23.0 Hz). HRMS
4.1.3.9.
Yield 26%. 1H NMR (400 MHz, Acetone-d6
1H), 7.58 – 7.50 (m, 2H), 7.36 (dt, = 10.5, 9.0 Hz, 1H), 3.68 – 3.60 (m, 1H), 3.57 – 3.49 (m, 1H), 3.30 – 3.20 (m, 1H), 1.96 – 1.79
(m, 3H), 1.72 – 1.53 (m, 5H), 1.44 – 1.34 (m, 2H). 13C NMR (101 MHz, Acetone-d6
161.7 (d, = 256.4 Hz), 161.2, 149.6 (dd,
= 244.1, 13.2 Hz), 146.6 (dd, = 243.1, 12.6 Hz), 135.6 (dd, = 9.0, 3.0 Hz), 135.4 (d, = 3.4 Hz), 132.2 (d, = 10.0 Hz), 129.9 (d,
= 3.9 Hz), 124.6 (d, = 15.7 Hz), 117.5 (d, = 24.2 Hz), 117.5 – 117.1 (m), 116.5 – 116.1 (m), 109.3 (d, = 22.2 Hz), 59.6, 47.3,
37.7, 29.7, 27.3, 25.9, 22.9, 21.0. 19F NMR (377 MHz, Acetone-d6
-110.3 – -110.4 (m), -139.6 – -139.7 (m), -146.2 – -146.3 (m).
HRMS (ESI): m/z [M+H]+ calcd for C21H21F3N2O3S: 439.1303, found: 439.1297.
N-(3,4-Difluorophenyl)-2-fluoro-5-((octahydro-1H-indol-1-yl)sulfonyl)benzamide (4i)
)
δ
9.89 (s, 1H), 8.26 (dd, = 6.6, 2.4 Hz, 1H), 8.14 – 8.06 (m, 1H), 8.02 – 7.94 (m,
J
J
)
δ
J
J
J
J
J
J
J
J
J
J
)
δ
4.1.3.10.
Yield 69%. 1H NMR (400 MHz, DMSO-d6
7.62 (m, 1H), 7.52 – 7.44 (m, 2H), 7.44 – 7.35 (m, 1H), 7.30 – 7.23 (m, 2H), 7.18 – 7.04 (m, 3H), 1.53 (s, 6H). 13C NMR (101 MHz,
DMSO-d6 161.9, 160.7 (d, = 255.4 Hz), 149.4 (dd, = 243.6, 13.2 Hz), 146.3 (dd, = 242.5, 12.6 Hz), 145.5, 140.2 (d, = 3.3
Hz), 136.0 (dd, = 8.8, 2.9 Hz), 131.3 (d, = 9.9 Hz), 129.0 (d, = 3.9 Hz), 128.1, 126.9, 126.1, 124.7 (d, = 16.3 Hz), 118.0 (d,
= 17.8 Hz), 117.4 (d, = 23.7 Hz), 116.9 (dd, = 6.2, 3.3 Hz), 109.5 (d,
= 21.6 Hz), 58.1, 30.2. 19F NMR (377 MHz, Acetone-d6
N-(3,4-Difluorophenyl)-2-fluoro-5-(
N-(2-phenylpropan-2-yl)sulfamoyl)benzamide (4j)
)
δ
10.69 (s, 1H), 8.25 (s, 1H), 8.05 – 7.82 (m, 1H), 7.75 (dd,
J = 6.5, 2.4 Hz, 1H), 7.74 –
)
δ
J
J
J
J
J
J
J
J
J
J
J
J
)
11