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V. V. Solomin et al.
Letter
Synlett
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(26) Quinazolin-2-amine (3); Typical Procedure
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A mixture of guanidine hydrochloride (2a; 765 mg, 8 mmol)
and KOH (441 mg, 8 mmol) was dissolved in MeOH (30 mL) and
the mixture was stirred for 10 min at r.t. (2-Formylphe-
nyl)boronic acid (1; 400 mg, 2.67 mmol) was added in one
portion followed by CuI (76 mg, 0.4 mmol), and the resulting
mixture was heated at 70 °C overnight. The mixture was then
concentrated under reduced pressure and partitioned between
aq NH3 (30 mL) and EtOAc (120 mL). The organic layer washed
with brine, dried (Na2SO4), and concentrated under reduced
pressure. The crude product was purified by trituration with
EtOAc (3 mL) to give a slightly beige solid; yield: 198 mg (51%);
mp 194–196 °C.
1H NMR (400 MHz, DMSO-d6): = 9.10 (s, 1 H), 7.78 (d, J = 8.9
Hz, 1 H), 7.67 (t, J = 8.5 Hz, 1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.21 (t,
J = 7.9 Hz, 1 H), 6.82 (s, 2 H). 13C NMR (101 MHz, DMSO-d6): =
162.4, 160.9, 151.2, 134.1, 127.9, 124.5, 122.0, 119.5. LC/MS:
m/z [M + H]+ calcd for C8H8N3: 146.17; found: 146.16. The spec-
tral data correspond to the reported values (see Ref. 10).
N-Methylquinazolin-2-amine (5a)
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Prepared from (2-Formylphenyl)boronic acid (1) and N-methyl-
guanidine hydrochloride (4a), and purified by column chroma-
tography [silica gel, EtOAc–PE (20 to 50% gradient)] as a yellow-
ish solid: yield: 134 mg (63%); mp 81–83 °C; Rf = 0.63 (EtOAc).
1H NMR (400 MHz, CDCl3): = 9.03 (s, 1 H), 7.72–7.56 (m, 3 H),
7.22 (t, J = 7.9 Hz, 1 H), 5.43 (br s, 1 H), 3.12 (d, J = 4.0 Hz, 3 H).
13C NMR (101 MHz, CDCl3): = 162.01, 160.50, 152.44, 134.37,
127.79, 125.83, 122.72, 120.75, 28.77. HRMS: m/z [M + H]+ calcd
for C9H10N3: 160.0875; found: 160.0881.
6-(Benzyloxy)-N-methylquinazolin-2-amine (8b)
Prepared from boronic acid 6b and N-methylguanidine hydro-
chloride (4a), and purified by column chromatography [silica
gel, EtOAc–PE (20 to 60% gradient)] as a yellowish solid; yield:
150 mg (57%); mp 130–132 °C, Rf = 0.38 (50% EtOAc–PE).
1H NMR (400 MHz, CDCl3): = 8.88 (s, 1 H), 7.58 (d, J = 9.2 Hz, 1
H), 7.51–7.32 (m, 6 H), 7.05 (d, J = 2.8 Hz, 1 H), 5.23 (s, 1 H), 5.12
(s, 2 H), 3.10 (d, J = 5.1 Hz, 3 H). 13C NMR (101 MHz, CDCl3): =
160.67, 159.78, 154.12, 148.30, 136.70, 128.80, 128.28, 127.67,
127.23, 127.13, 120.32, 106.82, 70.55, 28.76. HRMS: m/z [M +
H]+ calcd for C16H16N3O: 266.1293; found: 266.1292.
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Synlett 2020, 31, A–D