Journal of Medicinal Chemistry
Article
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74.48 (s, CH2N), 52.37 (s, N(CH3)2), 46.88 (s, SCH3, JCPt = 92.4 Hz).
19F{1H} NMR (282.40 MHz, CDCl3): δ −114.45 (s, F, JFPt = 56.5
Hz). 195Pt NMR (86.18 MHz, CDCl3): δ −3630.71 (s). ESI-MS (pos.
ion mode, CH2Cl2): m/z 425.06 ([M − Cl]+, calcd. 425.06).
Complex 9a. White solid. Yield: 57%. Anal. Calcd for 9a
C11H17ClFNOPtS: C, 28.67; H, 3.72; N, 3.04; S, 6.96. Found: C,
28.70; H, 3.73; N, 3.01; S, 6.99. 1H NMR (400 MHz, CDCl3): δ 7.91
(dd, 1H, H6, JH6H5 ≈ JHF = 8.4 Hz, JHPt = 45.6 Hz), 6.78 (m, 2H,
H3+H5), 3.97 (s, 2H, CH2N, JHPt = 39.6 Hz), 3.55 (s, 6H, SCH3, JHPt
=2 4.0 Hz), 2.93 (s, 6H, N(CH3)2, JHPt = 32.8 Hz). 13C{1H} NMR
(75.46 MHz, CDCl3): δ 135.46 (s, CH6, JCPt = 36.2 Hz), 112.55 (d,
CH5, JCF = 19.2 Hz, JCPt = 61 Hz), 108.83 (d, CH3, JCF = 21.5 Hz, JCPt
= 61.6 Hz), 74.32 (d, CH2N, JCF = 2.5 Hz, JCPt = 49 Hz), 52.17 (s,
N(CH3)2), 46.65 (s, SCH3, JCPt = 62.9 Hz). 19F{1H} NMR (282.40
MHz, CDCl3): δ −118.56 (s, F, JFPt = 11.3 Hz). 195Pt NMR (86.18
MHz, CDCl3): δ −3656.58 (s). ESI-MS (pos. ion mode, CH2Cl2): m/
z 425.06 ([M − Cl]+, calcd. 425.06).
Complex 10a. White solid. Yield: 21%. Anal. Calcd for 10a
C12H17ClF3NOPtS: C, 28.21; H, 3.35; N, 2.74; S, 6.28. Found: C,
28.25; H, 3.34; N, 2.72; S, 6.29. 1H NMR (300 MHz, CDCl3): δ 8.28
(s, 1H, H6, JHPt = 50.3 Hz), 7.33 (d, 1H, H4, JH4H3 = 7.8 Hz), 7.14 (d,
1H, H3, JH3H4 = 7.8 Hz), 4.01 (s, 2H, CH2N, JHPt = 39.6 Hz), 3.55 (s,
6H, SCH3, JHPt = 24.9 Hz), 2.93 (s, 6H, N(CH3)2, JHPt = 33.6 Hz).
13C{1H} NMR (75.46 MHz, CDCl3): δ 130.98 (s, CH6), 121.51 (m,
CH3+CH4), 74.74 (s, CH2N, JCPt = 52.8 Hz), 52.52 (s, N(CH3)2),
46.88 (s, SCH3, JCP = 62.4 Hz). 19F{1H} NMR (282.40 MHz, CDCl3):
δ −62.18 (s, CF3). 195Pt NMR (86.18 MHz, CDCl3): δ −3629.23 (s).
ESI-MS (pos. ion mode, CH2Cl2): m/z 475.06 ([M − Cl]+, calcd.
425.06).
Complex 11a. White solid. Yield: 22%. Anal. Calcd for 11a
C12H17ClF3NOPtS: C, 28.21; H, 3.35; N, 2.74; S, 6.28. Found: C,
28.22; H, 3.34; N, 2.72; S, 6.25. 1H NMR (300 MHz, CDCl3): δ 8.07
(m, 1H, H6, JHPt = 47.1 Hz), 7.27 (m, 2H, H3+H5), 4.01 (s, 2H,
CH2N, JHPt = 40.5 Hz), 3.55 (s, 6H, SCH3, JHPt = 24.9 Hz), 2.92 (s,
6H, N(CH3)2, JHPt = 33.6 Hz). 13C{1H} NMR (75.46 MHz, CDCl3):
δ 134.47 (s, CH6, JCPt = 54.3 Hz), 122.60 (s, CH5, JCPt = 55.1 Hz),
117.88 (s, CH3, JCPt = 21.1 Hz), 74.42 (s, CH2N, JCPt = 51.5 Hz), 52.17
(s, N(CH3)2), 46.61 (s, SCH3, JCPt = 62.3 Hz). 19F{1H} NMR (282.40
MHz, CDCl3): δ −62.21 (s, CF3). 195Pt NMR (86.18 MHz, CDCl3): δ
−3629.08 (s). ESI-MS (pos. ion mode, CH2Cl2): m/z 475.06 ([M −
Cl]+, calcd. 425.06).
3.04; N, 1.64. H NMR (400 MHz, CDCl3): δ 7.86 (m, 6H, Hortho
PAr3), 7.67 (d, 6H, Hmeta PAr3, JHmHo = 7.6 Hz), 7.01 (d, 1H, H3, JH3H4
= 8.4 Hz), 6.45 (dd, 1H, H4, JH4H3 = 8.4 Hz, JH4H6 = 2.4 Hz), 5.83 (d,
1H, H6, JH6H4 = 2.4 Hz, JHPt = 59.6 Hz), 4.08 (d, 2H, CH2N, JHP = 2.4
Hz, Pt satellites are observed as shoulders), 3.07 (s, 3H, OCH3), 2.97
(d, 6H, N(CH3)2, JHP= 2.8 Hz, Pt satellites are observed as shoulders).
13C{1H} NMR (150.9 MHz, CDCl3): δ 135.61 (d, CHortho PAr3, JCP
=
17.4 Hz), 125.32 (m, CHmeta PAr3), 122.93 (s, CH3), 122.81 (d, CH6,
JCP = 9.8 Hz), 109.94 (s, CH4), 74.17 (s, CH2N), 54.75 (s, OCH3),
51.07 (s, N(CH3)2). 31P{1H} NMR (162.29 MHz, CDCl3): δ 21.59 (s,
JPPt = 4301.2 Hz). 19F{1H} NMR (282.40 MHz, CDCl3): δ −63.08 (s,
CF3 PAr3). 195Pt NMR (86.18 MHz, CDCl3): δ −4051.79 (d, JPtP
=
4301.2 Hz). ESI-MS (pos. ion mode, CH2Cl2): m/z 825.13 ([M −
Cl]+, calcd. 825.13).
Complex 3b. White solid. Yield: 78%. Anal. Calcd for 3b
C31H26ClF9NOPPt: C, 43.24; H, 3.04; N, 1.63. Found: C, 43.26; H,
1
3.03; N, 1.65. H NMR (300 MHz, CDCl3): δ 7.85 (m, 6H, Hortho
PAr3), 7.65 (d, 6H, Hmeta PAr3, JHmHo = 7.0 Hz), 6.69 (d, 1H, H3, JHP
=
2.7 Hz), 6.15 (dd, 1H, H6, JH6H5 = 8.4 Hz, JHP = 3.0 Hz, Pt satellites are
observed as shoulders), 6.01 (dd, 1H, H5, JH5H6 = 8.4 Hz, JHP= 2.7 Hz),
4.09 (d, 2H, CH2N, JHP = 3.0 Hz, JHPt = 30.3 Hz), 3.66 (s, 3H, OCH3),
2.98 (d, 6H, N(CH3)2, JHP = 3.0 Hz, JHPt = 25.8 Hz). 13C{1H} NMR
(75.46 MHz, CDCl3): δ 137.4 (d, CH6, JCP = 6.2 Hz, JCPt = 86.5 Hz),
135.32 (d, CHortho PAr3, JCP = 11.6 Hz), 124.94 (m, CHmeta PAr3),
110.77 (s, CH5, JCPt = 69.9 Hz), 108.63 (s, CH3), 74.42 (d, CH2N, JCP
= 3.2 Hz, JCPt = 44.3 Hz), 54.90 (s, OCH3), 50.94 (s, N(CH3)2, JCPt
=
=
2.5 Hz). 31P{1H} NMR (162.29 MHz, CDCl3): δ 21.66 (s, JPPt
4355.6 Hz). 19F{1H} NMR (282.40 MHz, CDCl3): δ −62.76 (s, CF3
PAr3). 195Pt NMR (86.18 MHz, CDCl3): δ −4093.11 (d, JPtP =4355.6
Hz). ESI-MS (pos. ion mode, CH2Cl2): m/z 825.13 ([M − Cl]+, calcd.
825.13).
Complex 4b. White solid. Yield: 14%. Anal. Calcd for 4b
C31H26ClF9NPPt: C, 44.06; H, 3.10; N, 1.66. Found: C, 44.05; H,
1
3.11; N, 1.67. H NMR (400 MHz, CDCl3): δ 7.86 (m, 6H, Hortho
PAr3), 7.66 (d, 6H, Hmeta PAr3, JHmHo = 7.2 Hz), 6.95 (d, 1H, H3, JH3H4
= 7.6 Hz), 6.69 (d, 1H, H4, JH4H3 = 7.6 Hz), 5.99 (s, 1H, H6, JHPt
=
54.8 Hz), 4.08 (d, 2H, CH2N, JHP = 2.8 Hz, JHPt = 29.6 Hz), 2.98 (d,
6H, N(CH3)2, JHP = 2.8 Hz, Pt satellites are observed as shoulders),
1.67 (s, 3H, CH3). 13C{1H} NMR (75.46 MHz, CDCl3): δ 138.0 (d,
CH6, JCP = 5.6 Hz), 135.44 (d, CHortho PAr3, JCP = 11.5 Hz), 125.04
(m, CHmeta PAr3), 124.35 (s, CH4), 121.83 (s, CH3), 74.34 (s, CH2N),
50.92 (s, N(CH3)2), 20.80 (s, CH3). 31P{1H} NMR (121.5 MHz,
CDCl3): δ 20.89 (s, JPPt = 4321.3 Hz). 19F{1H} NMR (282.40 MHz,
CDCl3): δ −63.17 (s, CF3 PAr3). 195Pt NMR (86.18 MHz, CDCl3): δ
−4060.36 (d, JPtP = 4321.3 Hz). ESI-MS (pos. ion mode, CH2Cl2): m/
z 809.13 ([M − Cl]+, calcd. 809.13).
Complex 12a. Beige solid. Yield: 18%. Anal. Calcd for 12a
C11H17ClN2O3PtS: C, 27.08; H, 3.51; N, 5.74; S, 6.57. Found: C,
27.10; H, 3.54; N, 5.72; S, 6.56. 1H NMR (400 MHz, CDCl3): δ 8.88
(d, 1H, H6, JH6H4 = 2.4 Hz, JHPt = 53.2 Hz), 7.95 (dd, 1H, H4, JH4H3
=
8.4 Hz, JH4H6 = 2.4 Hz), 7.19 (d, 1H, H3, JH3H4 = 8.4 Hz), 4.05 (s, 2H,
CH2N, JHPt = 38.8 Hz), 3.58 (s, 6H, SCH3, JHPt = 23.6 Hz), 2.95 (s,
6H, N(CH3)2, JHPt = 32 Hz).13C{1H} NMR (150.9 MHz, CDCl3): δ
128.90 (s, CH6), 122.07 (s, CH3), 120.18 (s, CH4), 74.50 (s, CH2N,
JCPt = 75.5 Hz), 52.59 (s, N(CH3)2), 46.83 (s, SCH3, JCPt = 91.3 Hz).
195Pt NMR (86.18 MHz, CDCl3): δ −3606.56 (s). ESI-MS (pos. ion
Complex 5b. White solid. Yield: 92%. Anal. Calcd for 5b
C31H26ClF9NPPt: C, 44.06; H, 3.10; N, 1.66. Found: C, 44.08; H,
1
3.11; N, 1.64. H NMR (400 MHz, CDCl3): δ 7.81 (m, 6H, Hortho
PAr3), 7.66 (d, 6H, H3, Hmeta PAr3, JHmHo = 7.2 Hz), 6.93 (s, 1H, H3),
6.20 (m, 2H, H5+H6), 4.09 (d, 2H, CH2N, JHP = 2.8 Hz, JHPt = 29.2
Hz), 2.99 (d, 6H, N(CH3)2, Pt satellites are observed as shoulders),
2.13 (s, 3H, CH3).13C{1H} NMR (150.9 MHz, CDCl3): δ 137.13 (d,
CH6, JCP = 6.0 Hz, JCPt = 86.0 Hz), 135.62 (d, CHortho PAr3, JCP = 17.2
Hz), 126.60 (s, CH5, JCPt = 69.0 Hz), 125.22 (m, CHmeta PAr3), 123.35
(s, CH3), 74.72 (s, CH2N), 51.19 (s, N(CH3)2), 21.00 (s, CH3).
31P{1H} NMR (162.29 MHz, CDCl3): δ 21.78 (s, JPPt = 4316.2 Hz).
19F{1H} NMR (282.40 MHz, CDCl3): δ −62.77 (s, CF3 PAr3). 195Pt
NMR (86.18 MHz, CDCl3): δ −4084.98 (d, JPtP = 4316.2 Hz). ESI-
MS (pos. ion mode, CH2Cl2): m/z 809.13 ([M − Cl]+, calcd. 809.13).
Complex 6b. White solid. Yield: 66%. Anal. Calcd for 6b
C30H23BrClF9NPPt: C, 39.60; H, 2.55; N, 1.54. Found: C, 39.60; H,
2.61; N, 1.54.1H NMR (400 MHz, CDCl3): δ 7.83 (m, 6H, Hortho
PAr3), 7.69 (dd, 6H, Hmeta PAr3, JHmHo = 8.0 Hz, JHP = 1.6 Hz), 7.00
(dd, H4, JH4H3 = 8.0 Hz, JH4H6 = 2.0 Hz), 6.94 (d, 1H, H3, JH3H4 = 8.0
Hz), 6.23 (m, 1H, H6, JHPt= 57.6 Hz), 4.05 (d, 2H, CH2N, JHP = 3.2
Hz, JHPt = 28.4 Hz), 2.96 (d, 6H, N(CH3)2, JHP= 3.2 Hz, Pt satellites
are observed as shoulders). 13C{1H} NMR (150.9 MHz, CDCl3): δ
139.06 (d, CH6, JCP = 8.9 Hz), 135.56 (d, CHortho PAr3, JCP = 17.2 Hz),
126.65 (s, CH4), 125.43 (dd, CHmeta PAr3, JCP = 17.1 Hz, JCF = 5.6
mode, CH2Cl2): m/z 452.06 ([M − Cl]+, calcd. 452.06).
Complex 13a. Pale yellow solid. Yield: 14%. Anal. Calcd for 13a
C11H17ClN2O3PtS: C, 27.08; H, 3.51; N, 5.74; S, 6.57. Found: C,
27.09; H, 3.54; N, 5.73; S, 6.58. 1H NMR (400 MHz, CDCl3): δ 8.16
(m, 1H, H6, JHPt = 46.4 Hz), 7.89 (m, 2H, H3+H5), 4.06 (s, 2H,
CH2N, JHPt = 40.0 Hz), 3.58 (s, 6H, SCH3, JHPt = 23.6 Hz), 2.95 (s,
6H, N(CH3)2, JHPt = 32.8 Hz). 13C{1H} NMR (150.9 MHz, CDCl3):
δ 135.05 (s, CH6), 120.95 (s, CH5), 116.28 (s, CH3), 74.12 (s, CH2N),
52.32 (s, N(CH3)2), 46.71 (s, SCH3, JCPt= 91.3 Hz). 195Pt NMR (86.18
MHz, CDCl3): δ −3587.25 (s). ESI-MS (pos. ion mode, CH2Cl2): m/
z 452.06 ([M − Cl]+, calcd. 452.06).
General Procedure for the Synthesis of Cycloplatinated
Phosphine Pt(II) Complexes 1b−13b. The platinum DMSO
derivatives 1a−13a was converted into the corresponding tris(4-
trifluoromethyl-phenyl)phosphine derivatives 1b−13b via ligand
exchange.60 These can also be prepared from the chloride dinuclear
platinum complexes as we described previously.30
Complex 2b. White solid. Yield: 73%. Anal. Calcd for 2b
C31H26ClF9NOPPt: C, 43.24; H, 3.04; N, 1.63. Found: C, 43.25; H,
L
J. Med. Chem. XXXX, XXX, XXX−XXX