ACS Infectious Diseases
Article
Hydrazine; 2-Hydrazino-1,3-benzothiazole-5-carboxylic
acid (92). General Procedure B was followed using 91 (15
mg, 0.057 mmol). The reaction was concentrated and then
8.46 (dd, J = 1.3, 7.8 Hz, 1H), 7.92 (dd, J = 1.3, 7.9 Hz, 1H),
7.85−7.76 (m, 2H), 7.47 (t, J = 7.9 Hz, 1H), 7.45−7.33 (m,
2H), 7.22−7.08 (m, 1H), 2.94 (s, 3H). MS, m/z 301 (100) [M
1
+
lyophilized to obtain 92 as a solid (14 mg, 100%). H NMR
+ H] .
(
2
300 MHz, MeOD): δ 8.35−7.92 (m, 1H), 7.83−7.53 (m,
2-Methylsulfonyl-N-phenyl-1,3-benzothiazole-4-carboxa-
+
H). MS, m/z 210 (100) [M + H] .
mide (100). General Procedure E was followed using 99 (31
1
N-Methyl-2-methylsulfanyl-1,3-benzothiazole-4-carboxa-
mg, 0.10 mmol) to obtain 100 as a solid (28 mg, 79%). H
mide (93). HBTU (77 mg, 0.20 mmol) was added to a stirred
solution of 61 (35 mg, 0.16 mmol) in DMF (1 mL) under a N2
atmosphere followed by methanamine hydrochloride (14 mg,
NMR (300 MHz, CDCl ): δ 11.30 (br s, 1H), 8.71 (d, J = 7.6
3
Hz, 1H), 8.23 (d, J = 7.7 Hz, 1H), 7.92−7.68 (m, 3H), 7.43 (t,
J = 7.9 Hz, 2H), 7.25−7.12 (m, 1H), 3.48 (s, 3H). MS, m/z
+
0.21 mmol) and DIPEA (54 μL, 0.31 mmol). The solution was
333 (100) [M + H] .
then stirred for 3 h. The reaction was concentrated to dryness,
and the residue was dissolved in EtOAc (10 mL). The organic
solution was washed with water (2 × 15 mL) and saturated
brine solution (15 mL), dried with Na SO , and then
2-Hydrazino-N-phenyl-1,3-benzothiazole-4-carboxamide
(101). General Procedure B was followed using 100 (28 mg,
1
0.083 mmol) to obtain 101 as a solid (16 mg, 66%). H NMR
(300 MHz, DMSO-d ): δ 9.93 (s, 1H), 8.00 (dd, J = 1.3, 7.8
2
4
6
concentrated. The crude residue was then purified by column
Hz, 1H), 7.95−7.81 (m, 3H), 7.45−7.29 (m, 2H), 7.20−6.99
+
chromatography gradient eluting with 100% CyHex to 20%
(m, 3H), 5.37 (s, 2H). MS, m/z 285 (100) [M + H] .
1
EtOAc/CyHex to obtain 93 as a solid (25 mg, 67%). H NMR
N-Benzyl-2-methylsulfanyl-1,3-benzothiazole-4-carboxa-
mide (102). The procedure used for 93 was followed using 67
(25 mg, 0.11 mmol) and benzylamine (29 μL, 0.27 mmol) to
(
300 MHz, CDCl ): δ 9.73 (br s, 1H), 8.39 (dd, J = 1.3, 7.7
3
Hz, 1H), 7.87 (dd, J = 1.3, 8.0 Hz, 1H), 7.42 (t, J = 7.8 Hz,
H), 3.12 (d, J = 4.8 Hz, 3H), 2.83 (s, 3H). MS, m/z 239
1
1
obtain 102 as a solid (33 mg, 95%). H NMR (300 MHz,
+
(
100) [M + H] .
CDCl ): δ 10.14 (br s, 1H), 8.50−8.30 (m, 1H), 7.93−7.79
3
N-Methyl-2-methylsulfonyl-1,3-benzothiazole-4-carboxa-
(m, 1H), 7.49−7.24 (m, 7H), 4.76 (d, J = 5.1 Hz, 2H), 2.43 (s,
+
mide (94). General Procedure E was followed using 93 (25
3H). MS, m/z 315 (100) [M + H] .
1
mg, 0.10 mmol) to obtain 94 as a solid (27 mg, 96%). H
N-Benzyl-2-methylsulfonyl-1,3-benzothiazole-4-carboxa-
NMR (300 MHz, CDCl ): δ 9.02 (br s, 1H), 8.60 (dd, J = 1.3,
mide (103). General Procedure E was followed using 102 (33
mg, 0.11 mmol) to obtain 103 as a solid (22 mg, 61%). H
3
1
7
8
2
.7 Hz, 1H), 8.15 (dd, J = 1.3, 8.2 Hz, 1H), 7.74 (dd, J = 7.7,
.2 Hz, 1H), 3.44 (s, 3H), 3.14 (d, J = 4.9 Hz, 3H). MS, m/z
NMR (300 MHz, CDCl ): δ 9.50 (br s, 1H), 8.65 (dd, J = 1.2,
3
+
71 (100) [M + H] .
7.6 Hz, 1H), 8.18 (dd, J = 1.3, 8.2 Hz, 1H), 7.78 (dd, J = 7.7,
8.2 Hz, 1H), 7.51−7.28 (m, 6H), 4.80 (d, J = 5.2 Hz, 2H),
2
-Hydrazinyl-N-methylbenzo[d]thiazole-4-carboxamide
+
(
95). General Procedure B was followed using 94 (27 mg, 0.10
3.20 (s, 3H). MS, m/z 347 (100) [M + H] .
1
mmol) to obtain 95 as a solid (14 mg, 64%). H NMR (300
N-Benzyl-2-hydrazino-1,3-benzothiazole-4-carboxamide
MHz, DMSO-d ): δ 9.85 (br s, 1H), 9.58 (br s, 1H), 8.00−
(104). General Procedure B was followed using 103 (22 mg,
0.064 mmol) to obtain 104 as a solid (19 mg, 97%). H NMR
6
1
7
.75 (m, 2H), 7.16−7.02 (m, 1H), 5.23 (br s, 2H), 2.89 (d, J =
+
4
.0 Hz, 5H). MS, m/z 223 (100) [M + H] .
(300 MHz, MeOD): δ 8.06 (dd, J = 1.3, 7.8 Hz, 1H), 7.80 (dd,
J = 1.3, 7.8 Hz, 1H), 7.45−7.20 (m, 5H), 7.15 (t, J = 7.81 Hz,
N-(Cyclopropylmethyl)-2-methylsulfanyl-1,3-benzothia-
zole-4-carboxamide (96). The procedure used for 93 was
followed using 67 (35 mg, 0.16 mmol) and cyclopropyl
+
1H), 4.71 (s, 2H). MS, m/z 299 (100) [M + H] .
2-Methylsulfanyl-N-(2-phenylethyl)-1,3-benzothiazole-4-
carboxamide (105). The procedure used for 93 was followed
using 67 (35 mg, 0.16 mmol) and 2-phenylethanamine (25 μL,
methanamine (28 μL, 0.32 mmol) to obtain 96 as a solid (29
1
mg, 67%). H NMR (300 MHz, CDCl ): δ 9.93 (br s, 1H),
3
1
8
7
1
.37 (dd, J = 1.3, 7.7 Hz, 1H), 7.86 (dd, J = 1.3, 8.0 Hz, 1H),
0.20 mmol) to obtain 105 as a solid (44 mg, 86%). H NMR
.41 (t, J = 7.8 Hz, 1H), 3.44 (dd, J = 5.1, 7.1 Hz, 2H), 1.23−
(300 MHz, CDCl ): δ 8.40 (dd, J = 1.3, 7.7 Hz, 1H), 7.87 (dd,
3
.00 (m, 1H), 0.65−0.50 (m, 2H), 0.39−0.18 (m, 2H). MS,
J = 1.3, 8.0 Hz, 1H), 7.46−7.36 (m, 1H), 7.36−7.18 (m, 6H),
+
m/z 279 (100) [M + H] .
3.87 (dt, J = 5.8, 6.9 Hz, 2H), 3.00 (t, J = 6.9 Hz, 2H), 2.51 (s,
+
N-(Cyclopropylmethyl)-2-methylsulfonyl-1,3-benzothia-
zole-4-carboxamide (97). General Procedure E was followed
3H). MS, m/z 329 (100) [M + H] .
2-Methylsulfonyl-N-(2-phenylethyl)-1,3-benzothiazole-4-
using 96 (29 mg, 0.10 mmol) to obtain 97 as a solid (32 mg,
carboxamide (106). General Procedure E was followed using
1
1
00%). H NMR (300 MHz, CDCl ): δ 9.27 (br s, 1H), 8.60
105 (44 mg, 0.13 mmol) to obtain 106 as a solid (39 mg,
3
1
(
(
dd, J = 1.2, 7.6 Hz, 1H), 8.16 (dd, J = 1.2, 8.2 Hz, 1H), 7.76
dd, J = 7.6, 8.1 Hz, 1H), 3.55−3.35 (m, 5H), 1.23−1.02 (m,
H), 0.69−0.52 (m, 2H), 0.41−0.24 (m, 2H). MS, m/z 311
81%). H NMR (300 MHz, CDCl ): δ 8.62 (dd, J = 1.2, 7.6
3
Hz, 1H), 8.15 (dd, J = 1.3, 8.2 Hz, 1H), 7.75 (dd, J = 7.6, 8.1
Hz, 1H), 7.40−7.17 (m, 6H), 4.01−3.83 (m, 2H), 3.10 (s,
1
+
+
(
100) [M + H] .
3H), 3.03 (t, J = 6.7 Hz, 2H). MS, m/z 361 (100) [M + H] .
N-(Cyclopropylmethyl)-2-hydrazino-1,3-benzothiazole-4-
carboxamide (98). General Procedure B was followed using
2-Hydrazino-N-(2-phenylethyl)-1,3-benzothiazole-4-car-
boxamide (107). General Procedure B was followed using 106
9
7 (32 mg, 0.10 mmol) to obtain 98 as a solid (10 mg, 38%).
(31 mg, 0.086 mmol) to obtain 107 as a solid (19 mg, 72%).
1
1
H NMR (300 MHz, DMSO-d ): δ 10.06 (s, 1H), 9.60 (s,
H NMR (300 MHz, DMSO-d ): δ 10.10 (s, 1H), 9.55 (as,
6
6
1
H), 7.98−7.73 (m, 2H), 7.16−7.01 (m, 1H), 5.24 (s, 2H),
1H), 7.91 (dd, J = 1.3, 7.8 Hz, 1H), 7.84 (dd, J = 1.3, 7.8 Hz,
1H), 7.30 (d, J = 4.6 Hz, 3H), 7.24−7.16 (m, 1H), 7.08 (t, J =
7.7 Hz, 1H), 5.24 (br s, 2H), 3.66−3.49 (m, 2H), 2.96−2.84
1
.15−0.96 (m, 1H), 0.56−0.40 (m, 2H), 0.35−0.12 (m, 2H).
+
MS, m/z 263 (100) [M + H] .
+
2
-Methylsulfanyl-N-phenyl-1,3-benzothiazole-4-carboxa-
mide (99). The procedure used for 93 was followed using 67
35 mg, 0.16 mmol) and aniline (18 μL, 0.20 mmol) to obtain
(m, 2H). MS, m/z 313 (100) [M + H] .
2-Chloro-N-phenyl-thiazole-4-carboxamide (108). 2-
Chlorothiazole-4-carboxylic acid (50 mg, 0.31 mmol) was
(
9
1
9 as a solid (31 mg, 66%). H NMR (300 MHz, CDCl ): δ
dissolved in DCM (15 mL) and stirred under N . EDC·HCl
3
2
1
159
ACS Infect. Dis. 2021, 7, 1143−1163