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26.5; IR (KBr, cm−1) ν 3417, 2978, 1720, 1612, 1388, 1254, 1165,
1030, 926, 756, 532; HRMS calcd for C26H28N4NaO5 [M + Na]+
499.1957, found 499.1956; HPLC analysis (Daicel Chiralcel OD-H
column, n-Hexane/i-PrOH = 90:10, 0.9 mL/min, λ = 254 nm) tR =
11.5 min (major),14.2 min (minor).
6.24 (m, 1H), 5.99 (s, 1H), 3.19 (s, 3H), 1.11 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 174.4, 168.3, 153.5, 144.3, 144.2, 134.0, 132.4, 129.6,
129.1, 129.1, 128.9, 128.4, 128.1, 127.1, 127.0, 125.9, 124.6, 124.0,
122.9, 121.8, 110.2, 107.7, 80.3, 63.5, 47.0, 27.8, 26.5; IR (KBr, cm−1)
ν 3429, 2978, 1720, 1612, 1473, 1385, 1250, 1165, 1088, 922, 756,
522; HRMS calcd for C29H29N4O4 [M + H]+ 497.2189, found
497.2195; HPLC analysis (Daicel Chiralcel OD-H column, n-Hexane/
EtOH = 95:5, 0.5 mL/min, λ = 254 nm) tR = 28.1 min (major), 36.0
min (minor).
tert-Butyl((R)-3-((S)-1-(3-methoxyphenyl)-2-oxo-2-(1H-pyrazol-1-
yl)ethyl)-1-methyl-2-oxoindolin-3-yl)carbamate (3ah). Yield: 97%
20
(92 mg), white solid, mp 70.1−72.2 °C, [α]D + 21.4 (c 0.61,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.8 Hz, 1H),
7.60 (s, 1H), 7.29−7.21 (m, 2H), 7.04−6.90 (m, 4H), 6.85 (d, J = 8.4
Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 6.36−6.35 (m, 1H), 6.03 (s, 1H),
5.62 (s, 1H), 3.74 (s, 3H), 3.18 (s, 3H), 1.17 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 174.1, 167.6, 159.3, 153.6, 144.4, 144.1, 132.3, 129.4,
129.2, 128.9, 128.6, 123.8, 122.8, 121.9, 115.9, 114.4, 110.3, 107.8,
80.4, 62.7, 55.2, 53.2, 27.9, 26.5; IR (KBr, cm−1) ν 3421, 2978, 1720,
1612, 1493, 1385, 1254, 1165, 1088, 756; HRMS calcd for
C26H28N4NaO5 [M + Na]+ 499.1957, found 499.1953; HPLC analysis
(Daicel Chiralcel OD-H column, n-Hexane/i-PrOH = 80:20, 0.2 mL/
min, λ = 254 nm) tR = 41.1 min (major), 52.0 min (minor).
tert-Butyl((R)-1-methyl-3-((S)-1-(naphthalen-2-yl)-2-oxo-2-(1H-
pyrazol-1-yl)ethyl)-2-oxoindolin-3-yl)carbamate (3am). Yield: 96%
20
(95 mg), white solid, mp 129.8−130.7 °C, [α]D +40.5 (c 0.48,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 2.8 Hz, 1H),
7.88 (s, 1H), 7.82−7.76 (m, 3H), 7.58 (s, 1H), 7.48−7.45 (m, 3H),
7.25 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 7.2 Hz, 1H), 6.93 (t, J = 7.2 Hz,
1H), 6.74 (d, J = 8.0 Hz, 1H), 7.33−7.32 (m, 1H), 6.17 (s, 1H), 5.79
(s, 1H), 3.19 (s, 3H), 1.16 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
174.1, 167.8, 153.6, 144.4, 144.1, 133.0, 132.9, 129.9, 129.2, 129.0,
128.87, 128.5, 128.2, 128.0, 127.9, 127.5, 126.6, 126.3, 123.7, 122.0,
110.4, 107.8, 80.4, 62.9, 53.3, 27.9, 26.5; IR (KBr, cm−1) ν 3417, 2978,
1720, 1616, 1388, 1250, 1165, 1088, 926, 756; HRMS calcd for
C29H28N4NaO4 [M + Na]+ 519.2008, found 519.2005; HPLC analysis
(Daicel Chiralcel OD-H column, n-Hexane/i-PrOH = 80:20, 0.3 mL/
min, λ = 254 nm) tR = 29.4 min (major), 33.3 min (minor).
tert-Butyl((R)-3-((S)-1-(3-bromophenyl)-2-oxo-2-(1H-pyrazol-1-
yl)ethyl)-1-methyl-2-oxoindolin-3-yl)carbamate (3ai). Yield: 92%
20
(97 mg), white solid, mp 77.2−79.5 °C, [α]D + 61.5 (c 0.65,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 2.8 Hz, 1H),
6.54 (s, 1H), 6.53 (s, 1H), 6.39 (d, J = 8.0 Hz, 1H), 7.30−7.22 (m,
2H), 7.14−7.09 (m, 2H), 6.96 (t, J = 7.6 Hz, 1H), 6.71 (d, J = 7.6 Hz,
1H), 6.42−6.41 (m, 1H), 6.36 (s, 1H), 5.56 (s, 1H), 3.18 (s, 3H), 1.18
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 173.4, 167.4, 153.6, 144.7,
143.6, 133.3, 133.1, 131.6, 129.5, 129.3, 129.3, 129.0, 128.8, 123.3,
122.2, 122.0, 110.7, 107.9, 80.5, 63.1, 52.4, 27.9, 26.4; IR (KBr, cm−1)
ν 3421, 2978, 1720, 1616, 1473, 1388, 1254, 1165, 1088, 926, 756;
HRMS calcd for C25H26BrN4O4 [M + H]+ 525.1137, found 525.1134;
HPLC analysis (Daicel Chiralcel OD-H column, n-Hexane/i-PrOH =
90:10, 0.2 mL/min, λ = 254 nm) tR = 58.0 min (major), 69.6 min
(minor).
tert-Butyl((R)-1-methyl-2-oxo-3-((S)-2-oxo-2-(1H-pyrazol-1-yl)-1-
(thiophen-2-yl)ethyl)indolin-3-yl)carbamate (3an). Yield: 93% (84
mg), white solid, mp 102.3−103.9 °C, [α]D20 +72.7 (c 0.68, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.66 (s, 1H), 7.27−7.21
(m, 2H), 7.13 (d, J = 7.2 Hz, 1H), 7.02−6.89 (m, 3H), 6.72 (d, J = 7.6
Hz, 1H), 6.52 (s, 1H), 6.42 (s, 1H), 5.92 (s, 1H), 3.15 (s, 3H), 1.18 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 173.3, 167.4, 153.6, 144.6,
143.6, 131.8, 129.7, 129.2, 129.0, 128.8, 127.0, 126.4, 123.0, 122.1,
110.8, 107.8, 80.4, 63.1, 48.1, 27.9, 26.4; IR (KBr, cm−1) ν 3417, 2981,
1720, 1616, 1388, 1250, 1165, 1088, 922; HRMS calcd for
C23H24N4NaO4S [M + Na]+ 475.1416, found 475.1418; HPLC
analysis (Daicel Chiralpak AD-H column, n-Hexane/i-PrOH = 70:30,
0.9 mL/min, λ = 254 nm) tR = 12.6 min (major), 31.0 min (minor).
tert-Butyl((R)-5-fluoro-1-methyl-2-oxo-3-((S)-2-oxo-1-phenyl-2-
(1H-pyrazol-1-yl)ethyl)indolin-3-yl)carbamate (3ba). Yield: 93% (86
tert-Butyl((R)-3-((S)-1-(2-methoxyphenyl)-2-oxo-2-(1H-pyrazol-1-
yl)ethyl)-1-methyl-2-oxoindolin-3-yl)carbamate (3aj). Yield: 87%
20
(83 mg), white solid, mp 109.8−111.9 °C, [α]D −58.9 (c 0.44,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 2.8 Hz, 1H),
7.52 (s, 1H), 7.33−7.28 (m, 2H), 7.00 (d, J = 8.4 Hz, 1H), 6.96 (d, J =
7.2 Hz, 1H), 6.87−6.83 (m, 4H), 6.53 (d, J = 6.8 Hz, 1H), 6.30 (s,
1H), 6.28−6.27 (m, 1H), 4.03 (s, 3H), 3.24 (s, 3H), 1.26 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 175.3, 168.0, 156.9, 145.0, 144.1, 130.7,
129.9, 129.7, 128.9, 128.5, 128.5, 124.4, 121.4, 120.6, 120.5, 111.7,
109.9, 107.5, 79.9, 63.5, 56.1, 46.3, 27.9, 26.4; IR (KBr, cm−1) ν 3421,
2978, 1720, 1616, 1477, 1388, 1254, 1084, 926, 756, 532; HRMS calcd
for C26H28N4NaO5 [M + Na]+ 499.1957, found 499.1954; HPLC
analysis (Daicel Chiralcel OD-H column, n-Hexane/i-PrOH = 95:5,
0.5 mL/min, λ = 254 nm) tR = 54.6 min (major), 63.7 min (minor).
tert-Butyl((R)-3-((S)-1-(2-bromophenyl)-2-oxo-2-(1H-pyrazol-1-
yl)ethyl)-1-methyl-2-oxoindolin-3-yl)carbamate (3ak). Yield: 91%
20
mg), white solid, mp 99.1−100.9 °C, [α]D +42.3 (c 0.13, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 2.8 Hz, 1H), 7.61 (s, 1H),
7.39−7.35 (m, 2H), 7.32−7.30 (m, 3H), 6.95 (td, J = 8.8, 2.4 Hz, 1H),
6.80 (dd, J = 8.0, 2.4 Hz, 1H), 6.66 (dd, J = 8.4, 4.0 Hz, 1H), 6.37−
6.36 (m, 1H), 6.13 (s, 1H), 5.61 (s, 1H), 3.16 (s, 3H), 1.21 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 173.8, 167.6, 158.8 (d, J = 239.1 Hz),
153.4, 144.5, 140.1, 130.7, 130.3, 128.8, 128.7, 128.5, 115.2 (d, J = 23.4
Hz), 111.9 (d, J = 25.3 Hz), 110.5, 108.2 (d, J = 7.9 Hz), 80.6, 62.9,
53.2, 27.9, 26.6; IR (KBr, cm−1) ν 3429, 2981, 1720, 1624, 1500, 1388,
1034, 930, 775; HRMS calcd for C25H25FN4NaO4 [M + Na]+
487.1758, found 487.1759; HPLC analysis (Daicel Chiralpak AD-H
column, n-Hexane/i-PrOH = 85:15, 0.9 mL/min, λ = 254 nm) tR =
24.4 min (major), 55.7 min (minor).
20
(96 mg), white solid, mp 92.1−94.0 °C, [α]D +79.0 (c 0.66,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 2.8 Hz, 1H),
7.64 (s, 1H), 7.60 (dd, J = 8.0, 1.2 Hz, 1H), 7.51 (dd, J = 8.0, 1.2 Hz,
1H), 7.26−7.20 (m, 2H), 7.16−7.09 (m, 2H), 6.98 (s, 1H), 6.89 (t, J =
7.2 Hz, 1H), 6.75 (d, J = 7.6 Hz, 1H), 6.40−6.39 (m, 1H), 6.17(s,
1H), 3.22 (s, 3H), 1.17 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
173.1, 168.3, 153.7, 144.7, 143.6, 133.0, 130.8, 130.7, 129.9, 129.2,
129.2, 128.9, 127.0, 126.9, 123.1, 122.0, 110.7, 107.8, 80.3, 63.5, 50.7,
27.9, 26.4; IR (KBr, cm−1) ν 3413, 2978, 1720, 1612, 1473, 1385,
1254, 1165, 1088, 922, 752, 529; HRMS calcd for C25H25BrN4NaO4
[M + Na]+ 547.0957, found 547.0951; HPLC analysis (Daicel
Chiralcel OD-H column, n-Hexane/i-PrOH = 90:10, 0.5 mL/min, λ =
254 nm) tR = 24.5 min (major), 34.9 min (minor).
tert-Butyl((R)-5-chloro-1-methyl-2-oxo-3-((S)-2-oxo-1-phenyl-2-
(1H-pyrazol-1-yl)ethyl)indolin-3-yl)carbamate (3ca). Yield: 91% (88
mg), white solid, mp 97.8−99.9 °C, [α]D20 +11.6 (c 0.60, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 8.16 (d, J = 2.8 Hz, 1H), 7.61 (s, 1H),
7.38−7.34 (m, 2H), 7.33−7.30 (m, 3H), 7.22 (dd, J = 8.0, 2.0 Hz,
1H), 6.98 (d, J = 2.0 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 6.38−6.36 (m,
1H), 6.08 (s, 1H), 5.61 (s, 1H), 3.16 (s, 3H), 1.21 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 173.7, 167.5, 153.4, 144.5, 142.7, 130.7, 130.6,
130.4, 128.9, 128.9, 128.8, 128.5, 127.4, 124.2, 110.5, 108.7, 80.7, 62.7,
53.2, 28.0, 26.6; IR (KBr, cm−1) ν 3425, 2981, 1724, 1612, 1493, 1388,
1250, 1165, 1095, 926, 525; HRMS calcd for C25H25ClN4NaO4 [M +
Na]+ 503.1462, found 503.1468; HPLC analysis (Daicel Chiralpak
AD-H column, n-Hexane/i-PrOH = 80:20, 0.9 mL/min, λ = 254 nm)
tR = 15.6 min (major), 33.6 min (minor).
tert-Butyl((R)-1-methyl-3-((S)-1-(naphthalen-1-yl)-2-oxo-2-(1H-
pyrazol-1-yl)ethyl)-2-oxoindolin-3-yl)carbamate (3al). Yield: 84%
20
(83 mg), white solid, mp 154.7−156.3 °C, [α]D −75.2 (c 0.56,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 8.4 Hz, 1H),
tert-Butyl((R)-5-bromo-1-methyl-2-oxo-3-((S)-2-oxo-1-phenyl-2-
(1H-pyrazol-1-yl)ethyl)indolin-3-yl)carbamate (3da). Yield: 91% (96
mg), white solid, mp 105.3−107.4 °C, [α]D20 +18.9 (c 0.16, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 2.8 Hz, 1H), 7.61 (s, 1H),
8.10 (d, J = 2.8 Hz, 1H), 7.83 (t, J = 8.8 Hz, 2H), 7.65 (t, J = 7.2 Hz,
2H), 7.59 (d, J = 7.2 Hz, 1H), 7.43−7.38 (m, 2H), 7.28−7.25 (m,
1H), 6.93−6.87 (m, 2H), 6.81 (d, J = 7.6 Hz, 1H), 6.71 (s, 1H), 6.25−
4336
dx.doi.org/10.1021/jo500145w | J. Org. Chem. 2014, 79, 4332−4339