Chemistry of Heterocyclic Compounds 2021, 57(5), 554–559
(100). Found, %: C 60.37; H 4.11; N 35.39. C6H5N3.
Calculated, %: C 60.50; H 4.23; N 35.27.
δ, ppm: –120 (s, CHF2). Mass spectrum, m/z (Irel, %): 246
[M+H]+ (100). Found, %: C 63.81; H 3.59; N 17.28.
C13H9F2N3. Calculated, %: C 63.67; H 3.70; N 17.14.
4-Difluoromethyl-2-phenylimidazo[1,5-a]pyrimidine (6).
Purified by flash column chromatography (SiO2, eluent
hexane–EtOAc, 20:3). Yield 0.37 g (15%), yellow powder,
mp 113–114°С (hexane), Rf 0.56. 1H NMR spectrum
(400 MHz, CDCl3), δ, ppm (J, Hz): 6.83 (1H, t, J = 52.8,
CHF2); 7.23 (1H, s, H-3); 7.40–7.50 (3H, m, H-3',4',5');
7.77 (1H, s, H-8); 7.88–8.05 (2H, m, H-2',6'); 8.19 (1H, s,
H-6). 13C NMR spectrum (125 MHz, CDCl3), δ, ppm
(J, Hz): 105.1 (t, J = 7.5); 110.8 (t, J = 242.6, CHF2);
121.2; 124.4 (t, J = 2.5); 126.8 (2C); 129.0 (2C); 130.6;
133.2 (t, J = 25.1, C-4); 136.2; 139.1; 151.6. 19F NMR
spectrum (470 MHz, CDCl3): –123.1 (s, CHF2). Mass
spectrum, m/z (Irel, %): 246 [M+H]+ (100). Found, %:
C 63.49; H 3.62; N 17.22. C13H9F2N3. Calculated, %:
C 63.67; H 3.70; N 17.14.
Methyl 4-methylimidazo[1,5-a]pyrimidine-2-carboxylate
(8). Purified by flash column chromatography (SiO2, eluent
hexane–EtOAc, 20:3). Yield 0.57 g (30%), yellow powder,
mp 183–184°С (hexane), Rf 0.62. 1H NMR spectrum
(400 MHz, CDCl3), δ, ppm: 2.67 (3H, s, CH3); 4.00 (3H, s,
CO2CH3); 7.20 (1H, s, H-3); 7.96 (1H, s, H-8); 8.13 (1H, s,
H-6). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 17.9;
53.3; 106.7; 124.2; 124.5; 137.8; 139.6; 142.9; 164.5. Mass
spectrum, m/z (Irel, %): 192 [M+H]+ (100). Found, %:
C 56.42; H 4.62; N 22.11. C9H9N3O2. Calculated, %:
C 56.54; H 4.75; N 21.98.
3-Methylimidazo[1,5-a]pyrimidine (3b). Yield 0.67 g
1
(50%), yellow powder, mp 124–125°С (hexane). H NMR
spectrum (500 MHz, CDCl3), δ, ppm: 2.28 (3H, s, CH3);
7.59 (1H, s, H-8); 7.93–7.99 (2H, m, H-2,6); 8.04 (1H, s,
H-4). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 15.5;
117.8; 119.3; 124.5; 125.9; 137.8; 149.2. Mass spectrum,
m/z (Irel, %): 134 [M+H]+ (100). Found, %: C 63.29;
H 5.16; N 31.77. C7H7N3. Calculated, %: C 63.14; H 5.30;
N 31.56.
3-Chloroimidazo[1,5-a]pyrimidine (3c). Yield 1.00 g
1
(65%), yellow powder, mp 154–155°С (EtOH). H NMR
spectrum (500 MHz, DMSO-d6), δ, ppm: 7.69 (1H, s, H-8);
8.02 (1H, s, H-6); 8.08 (1H, s, H-2); 8.24 (1H, s, H-4).
13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 118.0;
120.9; 125.2; 126.1; 136.8; 145.4. Mass spectrum, m/z (Irel, %):
156 [M(37Cl)+H]+ (45), 154 [M(35Cl)+H]+ (100). Found, %:
C 46.78; H 2.55; N 27.51. C6H4ClN3. Calculated, %:
C 46.93; H 2.63; N 27.36.
3-Bromoimidazo[1,5-a]pyrimidine (3d). Yield 1.25 g
1
(63%), yellow powder, mp 148–149°С (EtOH). H NMR
spectrum (500 MHz, CDCl3), δ, ppm: 7.61 (1H, s, H-8);
7.96 (1H, s, H-6); 8.06 (1H, s, H-2); 8.32 (1H, s, H-4).
13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 105.2;
120.9; 125.0; 128.4; 136.6; 146.7. Mass spectrum, m/z (Irel, %):
200 [M(81Br)+H]+ (95), 198 [M(79Br)+H]+ (100). Found, %:
C 36.51; H 2.10; N 21.38. C6H4BrN3. Calculated, %:
C 36.39; H 2.04; N 21.22.
Ethyl imidazo[1,5-a]pyrimidine-3-carboxylate (3e).
Yield 1.53 g (80%), brown powder, mp 145–146°С
(EtOH). H NMR spectrum (500 MHz, DMSO-d6), δ, ppm
(J, Hz): 1.34 (3H, t, J = 7.0, CH2CH3); 4.35 (2H, q, J = 7.0,
CH2CH3); 7.58 (1H, s, H-8); 8.47 (1H, s, H-6); 8.50 (1H, s,
H-2); 9.43 (1H, s, H-4). 13C NMR spectrum (100 MHz,
DMSO-d6), δ, ppm: 14.6; 61.8; 111.7; 119.0; 128.8; 136.1;
137.9; 145.8; 163.8. Mass spectrum, m/z (Irel, %): 192
[M+H]+ (100). Found, %: C 56.71; H 4.66; N 22.16.
C9H9N3O2. Calculated, %: C 56.54; H 4.75; N 21.98.
Methyl 2-methylimidazo[1,5-a]pyrimidine-4-carboxylate
(9). Purified by flash column chromatography (SiO2, eluent
hexane–EtOAc, 20:3). Yield 0.57 g (30%), yellow powder,
mp 145–146°С (hexane), Rf 0.38. 1H NMR spectrum
(400 MHz, CDCl3), δ, ppm: 2.55 (3H, s, CH3); 4.00 (3H, s,
CO2CH3); 7.21 (1H, s, H-3); 7.62 (1H, s, H-8); 8.95 (1H, s,
H-6). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 24.5;
53.5; 113.6; 119.6; 127.0; 128.8; 139.7; 153.5; 161.6. Mass
spectrum, m/z (Irel, %): 192 [M+H]+ (100). Found, %:
C 56.71; H 4.60; N 21.89. C9H9N3O2. Calculated, %:
C 56.54; H 4.75; N 21.98.
1
2,4-Dimethylimidazo[1,5-a]pyrimidine (3f). Yield 0.85 g
1
(58%), yellow powder, mp 136–137°С (hexane). H NMR
Ethyl 4-isopropylimidazo[1,5-a]pyrimidine-2-carboxylate
(15). Yield 1.79 g (77%), yellow powder, mp 74–75°С
spectrum (400 MHz, CDCl3), δ, ppm: 2.41 (3H, s, 4-CH3);
2.49 (3H, s, 2-CH3); 6.25 (1H, s, H-3); 7.43 (1H, s, H-8);
7.83 (1H, s, H-6). 13C NMR spectrum (100 MHz, CDCl3),
δ, ppm: 17.5; 24.6; 108.8 (2C); 118.2; 122.3; 138.9; 155.5.
Mass spectrum, m/z (Irel, %): 148 [M+H]+ (100). Found, %:
C 65.44; H 6.00; N 28.74. C8H9N3. Calculated, %: C 65.29;
H 6.16; N 28.55.
2-Difluoromethyl-4-phenylimidazo[1,5-a]pyrimidine (5).
Purified by flash column chromatography (SiO2, eluent
hexane–EtOAc, 20:3). Yield 0.91 g (37%), yellow powder,
mp 119–120°С (hexane), Rf 0.24. 1H NMR spectrum
(400 MHz, CDCl3), δ, ppm (J, Hz): 6.52 (1H, t, J = 54.8,
CHF2); 6.82 (1H, s, H-3); 7.58–7.66 (3H, m, H-3',4',5');
7.69–7.76 (2H, m, H-2',6'); 7.82 (1H, s, H-8); 8.27 (1H, s,
H-6). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm
(J, Hz): 103.4; 113.9 (t, J = 239.2, CHF2); 122.1; 125.1;
127.8 (2C); 129.7 (2C); 131.1; 131.7; 138.2; 144.0; 148.8
(t, J = 27.8, C-2). 19F NMR spectrum (470 MHz, CDCl3),
1
(hexane). H NMR spectrum (500 MHz, CDCl3), δ, ppm
(J, Hz): 1.46 (3H, t, J = 7.0, CH2CH3); 1.49 (6H, d, J = 6.5,
CH(CH3)2); 3.29–3.35 (1H, m, J = 6.5, CH(CH3)2); 4.51
(2H, q, J = 7.0, CH2CH3); 7.30 (1H, s, H-3); 8.01 (1H, s,
H-8); 8.45 (1H, s, H-6). 13C NMR spectrum (100 MHz,
CDCl3), δ, ppm: 14.4; 19.6 (2C); 29.7; 62.5; 102.8; 124.0;
124.2; 138.1; 143.8; 149.5; 164.2. Mass spectrum, m/z (Irel, %):
234 [M+H]+ (100). Found, %: C 61.90; H 6.40; N 17.89.
C12H15N3O2. Calculated, %: C 61.79; H 6.48; N 18.01.
Ethyl 4-(tert-butyl)imidazo[1,5-a]pyrimidine-2-carboxy-
late (16). Yield 2.15 g (87%), yellow powder, mp 123°С
1
(hexane). H NMR spectrum (500 MHz, CDCl3), δ, ppm
(J, Hz): 1.44 (3H, t, J = 5.6, CH2CH3); 1.58 (9H, s, C(CH3)3);
4.50 (2H, q, J = 5.6, CH2CH3); 7.35 (1H, s, H-3); 8.03 (1H,
s, H-8); 8.75 (1H, s, H-6). 13C NMR spectrum (125 MHz,
CDCl3), δ, ppm: 14.6; 26.9 (3C); 35.8; 62.2; 103.8; 122.1;
128.7; 138.9; 143.9; 152.2; 164.2. Mass spectrum, m/z (Irel, %):
557