PAPER
Synthesis of Adamantylpyridin-2-amines
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to r.t., poured into H2O (200 mL), and extracted with benzene
(3 × 150 mL). The organic layers were combined and evaporated.
The residue was worked up with H2O (100 mL) and concd HCl (100
mL) to fully dissolve the residue. Then it was neutralized with 40%
aq NaOH and extracted with benzene (3 × 150 mL). After the sol-
vent had been evaporated, the residue was distilled under vacuum.
Yield: 221 mg (41%); pale yellow oil; chromatography (silica gel,
CH2Cl2–MeOH, 500:1 to 250:1).
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H), 1.10–
1.22 (m, 1 H), 1.50–1.72 (m, 12 H), 1.73–1.82 (m, 1 H), 1.95 (s, 3
H), 3.17 (t, J = 10.2 Hz, 1 H), 4.26 (d, J = 9.3 Hz, 1 H), 6.37 (d,
J = 8.6 Hz, 1 H), 6.42–6.47 (m, 1 H), 7.31–7.36 (m, 1 H), 8.00 (d,
J = 5.0 Hz, 1 H).
Yield: 32.8 g (85%); colorless liquid; bp 135–138 °C/20 Torr.
1H NMR (400 MHz, CDCl3): d = 0.89 (d, J = 6.3 Hz, 3 H), 0.96 (dd,
J = 14.0, 6.3 Hz, 1 H), 1.02 (dd, J = 14.0, 4.0 Hz, 1 H), 1.23 (br s, 2
H), 1.37 (s, 6 H), 1.45–1.55 (m, 6 H), 1.78 (s, 3 H), 2.88–2.96 (m, 1
H).
13C NMR (100.6 MHz, CDCl3): d = 26.55 (1 C), 28.34 (3 C), 32.17
(1 C), 36.74 (3 C), 42.01 (1 C), 42.72 (3 C), 54.98 (1 C).
13C NMR (100.6 MHz, CDCl3): d = 11.58 (1 C), 22.33 (1 C), 28.28
(3 C), 36.97 (3 C), 37.30 (1 C), 38.68 (3 C), 62.15 (1 C), 105.83 (1
C), 111.47 (1 C), 137.05 (1 C), 147.77 (1 C), 160.24 (1 C).
MS (MALDI-TOF): m/z [M+] calcd for C18H26N2: 270.21; found:
270.17.
N-[(1-Adamantyl)(phenyl)methyl]pyridin-2-amine (3d)
Compound 3d was obtained from 1d (964 mg, 4 mmol) and 2 (948
mg, 6 mmol) in the presence of Pd(dba)2 (92 mg, 4 mol%) and
BINAP (110 mg, 4.5 mol%).
Anal. Calcd for C13H23N: C, 80.76; H, 11.99; N, 7.25. Found: C,
80.58; H, 11.67; N, 6.98.
Amines 3a–f; General Procedure
A flask flushed with anhyd argon and equipped with a magnetic stir-
rer and condenser was charged with pyBr (2; 0.5 mmol), Pd(dba)2
(2–4 mol%), the phosphane ligand (2.5–4.5 mol%), the appropriate
amine 1a–f (0.5 mmol), and absolute 1,4-dioxane (5 mL). t-BuONa
(0.55 mmol) was added, and the mixture was stirred under reflux for
4–9 h, and then cooled down to r.t.; the 1,4-dioxane was evaporated
under vacuum, and the residue was chromatographed (silica gel,
CH2Cl2, then CH2Cl2–MeOH, 500:1 to 3:1).
Yield: 810 mg (64%); pale yellow oil; chromatography (silica gel,
CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 1.45–1.60 (m, 6 H), 1.63–1.75 (m,
6 H), 1.97 (s, 3 H), 4.05 (d, J = 7.6 Hz, 1 H), 5.35 (d, J = 7.6 Hz, 1
H), 6.11 (d, J = 8.3 Hz, 1 H), 6.44–6.48 (m, 1 H), 7.19–7.29 (m, 6
H), 8.00–8.02 (m, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 28.30 (3 C), 36.38 (1 C), 36.78
(3 C), 39.02 (3 C), 66.39 (1 C), 105.91 (1 C), 112.66 (1 C), 126.83
(1 C), 127.55 (2 C), 128.54 (2 C), 137.41 (1 C), 139.59 (1 C), 148.05
(1 C), 158.49 (1 C).
N-(1-Adamantylmethyl)pyridin-2-amine (3b)
Compound 3b was obtained from 1b (330 mg, 2 mmol) and 2 (316
mg, 2 mmol) in the presence of Pd(dba)2 (23 mg, 2 mol%) and
ligand L1 (20 mg, 2.5 mol%).
MS (MALDI-TOF): m/z [M+] calcd for C22H26N2: 318.21; found:
318.22.
Yield: 444 mg (92%); pale yellow oil; chromatography (silica gel,
CH2Cl2–MeOH, 500:1 to 200:1).
1H NMR (400 MHz, CDCl3): d = 1.56 (s, 6 H), 1.62–1.72 (m, 6 H),
1.98 (s, 3 H), 2.94 (d, J = 6.1 Hz, 2 H), 4.55 (br s, 1 H), 6.37 (d,
J = 8.3 Hz, 1 H), 6.48–6.53 (m, 1 H), 7.33–7.40 (m, 1 H), 8.03 (d,
J = 4.1 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 28.29 (3 C), 33.89 (1 C), 37.00
(3 C), 40.48 (3 C), 54.15 (1 C), 106.18 (1 C), 112.29 (1 C), 137.30
(1 C), 148.06 (1 C), 159.48 (1 C).
N-[1-(1-Adamantylmethyl)propyl]pyridin-2-amine (3e)
Compound 3e was obtained from 1e (828 mg, 4 mmol) and 2 (948
mg, 6 mmol) in the presence of Pd(dba)2 (92 mg, 4 mol%) and
BINAP (110 mg, 4.5 mol%).
Yield: 541 mg (48%); pale yellow oil; chromatography (silica gel,
CH2Cl2–MeOH, 1:0, then 250:1).
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 7.5 Hz, 3 H), 1.17 (dd,
J = 14.4, 8.6 Hz, 1 H), 1.32 (dd, J = 14.4, 2.6 Hz, 1 H), 1.44–1.58
(m, 8 H), 1.56–1.69 (m, 6 H), 1.90 (s, 3 H), 3.64–3.70 (m, 1 H), 4.24
(d, J = 8.3 Hz, 1 H), 6.30 (d, J = 8.3 Hz, 1 H), 6.48 (ddd, J = 7.1,
5.1, 0.8 Hz, 1 H), 7.37 (ddd, J = 8.7, 7.7, 2.0 Hz, 1 H), 8.04 (ddd,
J = 5.1, 2.1, 0.8 Hz, 1 H).
13C NMR (100.6 MHz, CDCl3): d = 9.73 (1 C), 28.62 (3 C), 29.53
(1 C), 32.38 (1 C), 36.96 (3 C), 42.95 (3 C), 48.00 (1 C), 50.02 (1
C), 106.04 (1 C), 111.91 (1 C), 137.31 (1 C), 148.29 (1 C), 158.03
(1 C).
MS (MALDI-TOF): m/z [M+] calcd for C16H22N2: 242.18; found:
242.20.
N-(1-Adamantylmethyl)-N-(2-pyridyl)pyridin-2-amine (4b)
Compound 4b was obtained as a byproduct in the synthesis of 3b
from 1b (83 mg, 0.5 mmol) and 2 (79 mg, 0.5 mmol) in the presence
of Pd(dba)2 (12 mg, 4 mol%) and BINAP (14 mg, 4.5 mol%).
Yield: 38 mg (24%); yellow oil; chromatography (silica gel,
CH2Cl2–MeOH, 200:1).
1H NMR (400 MHz, CDCl3): d = 1.48 (s, 6 H), 1.56–1.74 (m, 6 H),
1.84 (s, 3 H), 4.03 (s, 2 H), 6.77–6.81 (m, 2 H), 7.03 (d, J = 8.3 Hz,
2 H), 7.42–7.47 (m, 2 H), 8.27 (d, J = 3.8 Hz, 2 H).
13C NMR (100.6 MHz, CDCl3): d = 28.38 (3 C), 36.26 (1 C), 36.86
(3 C), 41.10 (3 C), 58.75 (1 C), 115.25 (2 C), 116.74 (2 C), 136.77
(2 C), 147.87 (2 C), 158.86 (2 C).
MS (MALDI-TOF): m/z [M + H+] calcd for C19H29N2: 285.23;
found: 285.19.
N-[1-(1-Adamantylmethyl)propyl]-N-(2-pyridyl)pyridin-2-
amine (4e)
Compound 4e was obtained as a byproduct in the synthesis of 3e
(isolated as a mixture with 3e; molar ratio 4e/3e ca. 1:1); chroma-
tography (silica gel, CH2Cl2–MeOH, 100:1).
MS (MALDI-TOF): m/z [M+] calcd for C21H25N3: 319.20; found:
319.25.
1H NMR (400 MHz, CDCl3): d = 0.85 (t, J = 7.3 Hz, 3 H), 1.32 (dd,
J = 14.7, 4.3 Hz, 1 H), 1.43–1.67 (m, 13 H), 1.81 (dd, J = 14.9, 6.8
Hz, 1 H), 1.85 (s, 3 H), 1.98 (ddd, J = 16.6, 9.1, 7.3 Hz, 1 H), 5.08–
5.10 (m, 1 H), 6.78 (ddd, J = 7.1, 4.8, 0.8 Hz, 2 H), 6.85 (d, J = 8.4
Hz, 2 H), 7.41 (ddd, J = 9.1, 7.0, 1.0 Hz, 2 H), 8.33 (ddd, J = 5.0,
2.0, 0.8 Hz, 2 H).
N-[1-(1-Adamantyl)propyl]pyridin-2-amine (3c)
Compound 3c was obtained from 1c (386 mg, 2 mmol) and 2 (395
mg, 2.5 mmol) in the presence of Pd(dba)2 (46 mg, 4 mol%) and
BINAP (55 mg, 4.5 mol%).
13C NMR (100.6 MHz, CDCl3): d = 11.69 (1 C), 28.55 (3 C), 29.33
(1 C), 32.59 (1 C), 36.90 (3 C), 42.43 (3 C), 48.66 (1 C), 54.95 (1
Synthesis 2007, No. 14, 2215–2221 © Thieme Stuttgart · New York