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pentylamine was isolated from moisture and carbon
dioxide and refluxed until complete conversion of the
starting pyrimidine derivative (TLC). After cooling the
reaction mixture to ambient, the precipitate was
filtered off, washed with 5 mL of n-BuOH, dried, and
recrystallized from MeCN. Yield 487 mg (60%), mp
202–204°С (CH3CN). 1Н NMR spectrum (400.16 MHz,
DMSO-d6), δ, ppm: 1.16 m (2Н, СН), 1.39 m (2Н,
(С5, pyrimidine), 118.80 (C1arom, JCF = 17.1 Hz), 129.48
t (C4arom, JCF = 10.5 Hz), 153.84 (С2,6, pyrimidine),
1
160.33 (С4, pyrimidine), 162.05 d (С2,6arom, JCF
=
2
248.5, JCF = 7.8 Hz). Found, %: C 65.00; H 5.89; N
8.38. C18H20F2N2O2. Calculated, %: C 64.66; H 6.03;
N 8.38.
1-(2,6-Difluorophenyl)cyclopropane-1-carboxylic
acid (5a). A mixture of 15.3 g (100 mmol) of 2-(2,6-
difluorophenyl)acetonitrile, 152.5 g (70 mL, 812 mmol)
of dibromoethane, and 32.7 g (144 mmol) of
Et3BnN+Cl– was isolated from moisture and carbon
dioxide and vigorously stirred at 60°С. A solution
prepared from 95 g (1430 mmol, ≈84.5%) of KOH and
95 mL of water was then added dropwise; the mixture
was stirred during 6 h at 60–65°C, and left overnight.
On the next day, the reaction mixture was extracted
with t-BuOMe (3×100 mL), the combined organic
fractions were evaporated, and residual water was
removed via azeotropic distillation with toluene. Then
60 mL of water and 40 mL of concentrated sulfuric
acid were added to the obtained 1-(2,6-difluorophenyl)-
cyclopropanecarbonitrile, and the mixture was refluxed
during 4 h. The reaction mass was cooled to ambient;
the precipitate was filtered off and dried. Yield 17.82 g
(90%), mp 156–157°С (toluene). IR spectrum, ν, cm–1:
412 s, 772 m, 946 m, 994 m, 1048 s, 1246 m, 1270 m,
1306 m, 1324 m, 1414 m, 1468 m, 1474 m, 1504 s,
eq
eq
С2,5Н2 , с-Pent), 1.54 m (2Н, С3,4Н2 , c-Pent), 1.6 m
ax
(2Н, СН), 1.61 s (3Н, 5-СН3), 1.63 m (2Н, С3,4Н2 ,
ax
c-Pent), 1.91 m (2Н, С2,5Н2 , c-Pent), 4.06 m (1Н,
3
СН, c-Pent), 6.08 br.d (1H, NH, JНН = 7.9 Hz), 7.01
3
d.d (2Н, C3,5Н, JНН = 7.9, 3JНF = 8.0 Hz), 7.33 m (1Н,
C4Н), 10.32 br.s (1Н, NH). 13С NMR spectrum
(100.62 MHz, DMSO-d6), δС, ppm: 9.14 (5-CH3),
15.28 (СН2, c-Pr), 20.59 (С, c-Pr), 23.17 (С3,4, c-Pent),
32.27 (С2,5, c-Pent), 51.88 (C1, c-Pent), 107.38 (С5,
pyrimidine), 111.55 d.d (С3,5arom, 2JCF = 19.2, 4JCF = 5.5 Hz),
2
119.39 t (С1arom, JCF = 16.5 Hz), 150.63 (С2, pyri-
1
3
midine), 162.04 d.d (С2,6arom, JCF = 251.3, JCF
=
8.7 Hz), 162.12 (С6, pyrimidine), 163.48 (С4, pyrimidine).
Found, %: C 65.81; H 5.98; N 11.94. C19H21F2N3O.
Calculated, %: C 66.07; H 6.13; N 12.17.
2-Butoxy-6-[1-(2,6-difluorophenyl)cyclopropyl]-
5-methylpyrimidin-4(3Н)-one (9). A mixture of 1 g
(3.1 mmol) of compound 8a, 10 mL of n-BuOH, and
4 mL (2.8 g, 38.4 mmol) of methylisopropylamine was
isolated from moisture and carbon dioxide and
refluxed until complete conversion of the starting
pyrimidine derivative (TLC). After the reaction was
complete, the solvent was distilled off under reduced
pressure. The residue was dissolved in THF, mixed
with silica gel, and evaporated to dryness. The
adsorbed product was transferred to a column and
eluted with a EtOAc–c-С6Н14 mixture (5→50% EtOAc
by volume). The fractions containing the target product
were combined, evaporated under reduced pressure,
and recrystallized from hexane. Yield 652 mg (63%),
mp 127–128°С (CH3CN). 1Н NMR spectrum
(400.16 MHz, DMSO-d6), δ, ppm: 0.90 t (3H,
1
1624 m, 1666 m, 1726 s. Н NMR spectrum (400.16
eq
MHz, DMSO-d6), δ, ppm: 1.18 m (2H, СН2 , c-Pr),
ax
1.58 m (2H, СН2 , c-Pr), 7.03 m (2H, С3,5H), 7.36 m
(1H, C4H), 12.54 br.s (1H, OH). Mass spectrum (EI),
m/z (Irel, %): 197.9 (100) [M]+, 153.0 (37) [M –
COOH)]+, 133.0 (35) [M – COOH – HF]+, 127.2 (32)
[2,6-F2C6H3CH2]+. Found, %: C 60.50; H 4.08.
C10H8F2O2. Calculated, %: C 60.61; H 4.07.
1-(2-Fluoro-6-chlorophenyl)cyclopropane-1-car-
boxylic acid (5b) was prepared similarly from 17 g
(100 mmol) of 2-(2-fluoro-6-chlorophenyl)acetonitrile.
1
Yield 19.9 g (93%), mp 165–166.5°С (toluene). Н
ax
NMR spectrum (400.16 MHz, DMSO-d6), δ, ppm:
CH3CH2CH2CH2, J = 7.5 Hz), 1.22 m (2Н, СН2 ,
eq
ax
1.21 s (2H, СН2 , c-Pr), 1.66 s (2H, CH2 , c-Pr), 7.19
d.d (1H, C4H, J1 0.8, J2 7.2 Hz), 7.29–7.37 m (2H,
С3,5H), 12.52 s (1H, COOH). 13C NMR spectrum
(100.62 MHz, DMSO-d6), δC, ppm: 17.80 d (CH2, c-
Pr, J = 10.8 Hz), 21.51 d (C, c-Pr, J = 6.4 Hz), 114.46
d (C4arom), 125.56 q (C3arom, J = 16.1, J = 3.3 Hz),
129.79 d (C5arom, J = 39.2 Hz), 136.75 d (C1, J =
19.6 Hz), 160.84 (C2arom), 163.31 (C6arom), 173.84
(COOH). Found, %: C 56.21; H 4.00. C10H8ClFO2.
Calculated, %: C 55.96; H 3.76.
с-Pr), 1.36 sextet (2Н, CH3CH2CH2CH2, J = 7.2 Hz),
eq
1.59 m (2Н, СН2 , с-Pr), 1.65 quintet (2Н,
CH3CH2CH2CH2, J1 6.8, J2 7.2 Hz), 1.71 s (3Н,
5-СН3), 4.28 t (3Н, CH3CH2CH2CH2, J = 6.8 Hz), 7.03
m (2Н, C3,5Н), 7.35 m (1Н, C4Н), 12.14 br.s (1Н, NH).
13C NMR spectrum (100.62 MHz, DMSO-d6), δС, ppm:
6
9.58 t (5-CH3, JCF = 2.4 Hz), 13.55 (CH3CH2CH2CH2),
15.29 (СН2, с-Pr), 18.42 (СН3СН2СН2СН2), 20.39 (С,
с-Pr), 30.09 (CH3CH2CH2CH2), 66.42 (CH3CH2CH2CH2),
111.75 d.d (С3,5arom, 1JCF = 19.4, 2JCF = 6.1 Hz), 113.29
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 2 2017