Journal of Medicinal Chemistry
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Hz, 3H). 13C NMR (DMSO-d6): δ 169.3, 140.8, 132.8, 130.8, 129.6,
52.4, 35.8, 26.6. Anal. (C16H15Cl2NOS) C, H, N.
2-((Bis(4-fluorophenyl)methyl)thio)-N-(cyclopropylmethyl)-
acetamide (4p). Compound 4p was synthesized from 2-((bis(4-
fluorophenyl)methyl)thio)acetic acid and cyclopropylmethylamine
according to general procedure C. The product 4p (320 mg, 92%
2-((Bis(4-bromophenyl)methyl)thio)-N-methylacetamide (4i).
Compound 4i was synthesized from 2-mercapto-N-methylacetamide
and bis(4-bromophenyl)methanol, 3d, at 60 °C according to general
procedure A. The product 4i (1.86 g, 74% yield) was obtained as a
1
yield) was obtained as a white solid. Mp: 103−105 °C. H NMR
(CDCl3): δ 7.35 (dd, J = 8.8, 5.2 Hz, 4H), 6.99−7.05 (m, 4H), 6.58
(br s, 1H), 5.16 (s, 1H), 3.11 (dd, J = 7.0, 5.4 Hz, 2H), 3.08 (s, 2H),
0.91−1.01 (m, 1H), 0.52−0.56 (m, 2H), 0.23 (q, J = 5.0 Hz, 2H). 13C
NMR (CDCl3): δ 167.9, 162.1 (1JCF = 248 Hz), 136.0 (4JCF = 3.0 Hz),
129.8 (3JCF = 8.1 Hz), 115.7 (2JCF = 21.4 Hz), 53.3, 44.6, 36.0, 10.7,
3.4. Anal. (C19H19F2NOS) C, H, N.
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white solid. Mp: 149−151 °C. H NMR (DMSO-d6): δ 7.86 (br s,
1H), 7.53 (dt, J = 8.4, 2.2 Hz, 4H), 7.35 (dt, J = 8.4, 2.2 Hz, 4H), 5.42
(s, 1H), 2.99 (s, 2H), 2.53 (sd, J = 4.8 Hz, 3H). 13C NMR (DMSO-
d6): δ 168.3, 140.2, 131.5, 130.2, 120.4, 51.6, 34.9, 25.7. Anal.
(C16H15Br2NOS) C, H, N.
2-((Bis(4-bromophenyl)methyl)thio)-N-(cyclopropylmethyl)-
acetamide (4q). Compound 4q was synthesized from 2-((bis(4-
bromophenyl)methyl)thio)acetic acid and cyclopropylmethylamine
according to the modified general procedure C. Purification by flash
column chromatography using 1:1 ethyl acetate/hexanes gave the pure
N-Allyl-2-(benzhydrylthio)acetamide (4j). Compound 4j was
synthesized from 2-(benzhydrylthio)acetic acid and allylamine
according to the modified general procedure C. The product 4j
(1.97 g, 86% yield) was obtained as a viscous yellow oil that solidified
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over time. Mp: 45−47 °C. H NMR (CDCl3): δ 7.40 (d, J = 7.2 Hz,
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product 4q (1.08 g, 94% yield) as a white solid. Mp: 84−85 °C. H
4H), 7.32 (t, J = 7.4 Hz, 4H), 7.25 (t, J = 8.0 Hz, 2H), 6.67 (br s, 1H),
5.77−5.86 (m, 1H), 5.19 (d, Jtrans = 17.6 Hz, 1H), 5.15 (d, Jcis = 10.6
Hz, 1H), 5.13 (s, 1H), 3.84 (tt, J = 5.6, 1.6 Hz), 3.14 (s, 2H). 13C
NMR (CDCl3): δ 168.0, 140.3, 133.8, 128.8, 128.2, 127.6, 116.8, 55.1,
42.1, 36.1. Anal. (C18H19NOS) C, H, N.
NMR (CDCl3): δ 7.49 (dt, J = 8.8, 2.2 Hz, 4H), 7.25 (dt, J = 8.4, 2.4
Hz, 4H), 6.56 (br s, 1H), 5.12 (s, 1H), 3.09 (dd, J = 7.2, 5.6 Hz, 2H),
3.07 (s, 2H), 0.88−0.97 (m, 1H), 0.53 (q, J = 6.6 Hz, 2H), 0.21 (q, J =
5.2 Hz, 2H). 13C NMR (CDCl3): δ 167.9, 139.0, 132.0, 130.0, 121.8,
53.5, 44.6, 35.9, 10.7, 3.5. Anal. (C19H19Br2NOS·1/4C4H8O2) C, H, N.
2-(Benzhydrylthio)-N-butylacetamide (4r). Compound 4r was
synthesized from 2-(benzhydrylthio)acetic acid and n-butylamine
according to the modified general procedure C. The product 4r
(264 mg, 87% yield) was obtained as a yellow oil. 1H NMR (CDCl3):
δ 7.39 (d, J = 7.2 Hz, 4H), 7.32 (t, J = 7.4 Hz, 4H), 7.24 (tt, J = 7.2, 1.7
Hz, 2H), 6.64 (br s, 1H), 5.11 (s, 1H), 3.21 (q, J = 6.7 Hz, 2H), 3.10
(s, 2H), 1.43−1.51 (m, 2H), 1.30−1.39 (m, 2H), 0.93 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3): δ 168.2, 140.5, 128.9, 128.3, 127.7, 55.1,
39.6, 31.7, 20.2, 13.9. Anal. (C19H23NOS) C, H, N.
2-(Benzhydrylthio)-N-propylacetamide (4k). Compound 4k was
synthesized from 2-(benzhydrylthio)acetic acid and propylamine
according to the modified general procedure C. The product 4k
(1.05 g, 91% yield) was obtained as a yellow oil that solidified over
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time. Mp: 57−58 °C. H NMR (CDCl3): δ 7.39 (d, J = 7.6 Hz, 4H),
7.32 (tt, J = 7.2, 1.6 Hz, 4H), 7.24 (t, J = 7.2 Hz, 2H), 6.64 (br s, 1H),
5.11 (s, 1H), 3.18 (q, J = 6.8 Hz, 2H), 3.11 (s, 2H), 1.47−1.56 (m,
2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (CDCl3): δ 168.2, 140.5,
128.9, 128.4, 127.7, 55.2, 41.6, 36.3, 22.9, 11.5. Anal. (C18H21NOS) C,
H, N.
2-((Bis(4-fluorophenyl)methyl)thio)-N-butylacetamide (4s). Com-
pound 4s was synthesized from 2-((bis(4-fluorophenyl)methyl)thio)-
acetic acid and n-butylamine according to general procedure C. The
product 4s (350 mg, 100%) was obtained as a white solid. Mp: 63−64
2-((Bis(4-fluorophenyl)methyl)thio)-N-propylacetamide (4l).
Compound 4l was synthesized from 2-((bis(4-fluorophenyl)methyl)-
thio)acetic acid and propylamine according to general procedure C.
The product 4l (320 mg, 95% yield) was obtained as a white solid.
Mp: 83−85 °C. 1H NMR (CDCl3): δ 7.32−7.37 (m, 4H), 6.99 −7.05
(m, 4H), 6.55 (br s, 1H), 5.14 (s, 1H), 3.20 (q, J = 6.6 Hz, 2H), 3.07
(s, 2H), 1.48−1.58 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13C NMR
(CDCl3): δ 168.0, 162.1 (1JCF = 247 Hz), 136.0 (4JCF = 3.7 Hz), 129.8
(3JCF = 8.1 Hz), 115.7 (2JCF = 21.4 Hz), 53.2, 41.5, 36.0, 22.8, 11.4.
Anal. (C18H19F2NOS) C, H, N.
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°C. H NMR (CDCl3): δ 7.34 (dd, J = 8.8, 5.2 Hz, 4H), 6.99−7.05
(m, 4H), 6.49 (br s, 1H), 5.13 (s, 1H), 3.24 (q, J = 6.6 Hz, 2H), 3.07
(s, 2H), 1.45−1.52 (m, 2H), 1.31−1.40 (m, 2H), 0.94 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3): δ 167.9, 162.1 (1JCF = 247 Hz), 136.0 (4JCF
= 3.7 Hz), 129.8 (3JCF = 8.1 Hz), 115.7 (2JCF = 21.4 Hz, 4C), 53.3,
39.5, 36.0, 31.6, 20.1, 13.7. Anal. (C19H21F2NOS) C, H, N.
2-((Bis(4-bromophenyl)methyl)thio)-N-butylacetamide (4t).
Compound 4t was synthesized from 2-((bis(4-bromophenyl)methyl)-
thio)acetic acid and n-butylamine according to the modified general
procedure C. Purification by flash column chromatography using 10%
MeOH/CHCl3 gave the pure product 4t (0.50 g, 88% yield) as a
2-((Bis(4-chlorophenyl)methyl)thio)-N-propylacetamide (4m).
Compound 4m was synthesized from 2-((bis(4-chlorophenyl)-
methyl)thio)acetic acid and propylamine according to the modified
general procedure C. The product 4m (2.06 g, 91% yield) was
obtained as a viscous yellow oil that solidified over time. Mp: 57−59
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yellow oil. H NMR (CDCl3): δ 7.45 (dt, J = 8.4, 2.0 Hz, 4H), 7.24
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°C. H NMR (CDCl3): δ 7.30 (s, 8H), 6.34 (br s, 1H), 5.11 (s, 1H),
(dt, J = 8.8, 2.4 Hz, 4H), 6.40 (br s, 1H), 5.07 (s, 1H), 3.22 (q, J = 6.8
Hz, 2H), 3.07 (s, 2H), 1.43−1.51 (m, 2H), 1.30−1.39 (m, 2H), 0.94
(t, J = 7.2 Hz, 3H). 13C NMR (CDCl3): δ 167.9, 139.1, 132.1, 130.0,
121.9, 53.7, 39.7, 36.1 31.7, 20.2, 13.9. Anal. (C19H21Br2NOS) C, H,
N.
2-(Benzhydrylthio)-N-(3-phenylpropyl)acetamide (4u). Com-
pound 4u was synthesized as previously described10 from 2-
(benzhydrylthio)acetic acid and 3-phenyl-1-propylamine according to
the modified general procedure C. Purification on a Teledyne ISCO
CombiFlash Rf instrument using 1:1 ethyl acetate/hexanes gave the
pure product 4u (1.66 g, 94% yield) as a white solid. Mp: 63−65 °C.
1H NMR (CDCl3): δ 7.37−7.39 (m, 4H), 7.28−7.33 (m, 6H), 7.16−
7.27 (m, 5H), 6.61 (br s, 1H), 5.10 (s, 1H), 3.24 (q, J = 6.8 Hz, 2H),
3.09 (s, 2H), 2.64 (t, J = 7.6 Hz, 2H), 1.78−1.86 (m, 2H). 13C NMR
(CDCl3): δ 168.3, 141.3, 140.5, 128.9, 128.6, 128.5, 128.3, 127.7,
126.2, 55.2, 39.5, 36.3, 33.4, 31.2. Anal. (C24H25NOS) C, H, N.
2-((Bis(4-fluorophenyl)methyl)thio)-N-(3-phenylpropyl)-
acetamide (4v). Compound 4v was synthesized from 2-((bis(4-
fluorophenyl)methyl)thio)acetic acid and 3-phenyl-1-propylamine
according to general procedure C. The product 4v (1.2 g, 100%)
was obtained as a yellow oil. 1H NMR (CDCl3): δ 7.26−7.35 (m, 6H),
7.16−7.22 (m, 3H), 6.98−7.04 (m, 4H), 6.48 (br s, 1H), 5.12 (s, 1H),
3.27 (q, J = 6.8 Hz, 2H), 3.04 (s, 2H), 2.66 (t, J = 7.8 Hz, 2H), 1.81−
3.20 (q, J = 6.8 Hz, 2H), 3.07 (s, 2H), 1.48−1.57 (m, 2H), 0.93 (t, J =
7.4 Hz, 3H). 13C NMR (CDCl3): δ 168.0, 138.6, 133.8, 129.7, 129.2,
53.6, 41.7, 36.1, 22.9, 11.5. Anal. (C18H19Cl2NOS) C, H, N.
2-((Bis(4-bromophenyl)methyl)thio)-N-propylacetamide (4n).
Compound 4n was synthesized from 2-((bis(4-bromophenyl)methyl)-
thio)acetic acid and propylamine according to the modified general
procedure C. The product 4n (1.75 g, 80% yield) was obtained as a
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light yellow solid. Mp: 92−94 °C. H NMR (CDCl3): δ 7.45 (d, J =
8.8 Hz, 4H), 7.24 (d, J = 8.8 Hz, 4H), 6.41 (br s, 1H), 5.08 (s, 1H),
3.19 (q, J = 6.8 Hz, 2H), 3.07 (s, 2H), 1.47−1.56 (m, 2H), 0.93 (t, J =
7.2 Hz, 3H). 13C NMR (CDCl3): δ 168.0, 139.1, 132.1, 130.0, 121.9,
53.7, 41.7, 36.1, 22.9, 11.5. Anal. (C18H19Br2NOS) C, H, N.
2-(Benzhydrylthio)-N-(cyclopropylmethyl)acetamide (4o). Com-
pound 4o was synthesized from 2-(benzhydrylthio)acetic acid and
cyclopropylmethylamine according to the modified general procedure
C. The product 4o (0.25 g, 94% yield) was obtained as a yellow oil. 1H
NMR (CDCl3): δ 7.41 (d, J = 7.6 Hz, 4H), 7.33 (tt, J = 7.4, 1.9 Hz,
4H), 7.25 (tt, J = 7.4, 1.7 Hz, 2H), 6.73 (br s, 1H), 5.14 (s, 1H), 3.12
(s, 2H), 3.09 (dd, J = 7.2, 5.6 Hz, 2H), 0.90−1.00 (m, 1H), 0.53 (q, J =
6.4 Hz, 2H), 0.22 (q, J = 5.2 Hz, 2H). 13C NMR (CDCl3): δ 168.1,
140.5, 128.9, 128.4, 127.7, 55.1, 44.7, 36.3, 10.8, 3.6. Anal.
(C19H21NOS) C, H, N.
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dx.doi.org/10.1021/jm401754x | J. Med. Chem. 2014, 57, 1000−1013