3.1. Chemistry
Commercial reagents were obtained from Sigma-Aldrich, Acros Organics, or Alfa Aesar and used without any further purification. All workup and purification procedures were carried out using analytical grade solvents. One-dimensional 1H, 19F, and 13C NMR spectra were acquired on a Bruker DRX-400 instrument (400, 376, and 101 MHz, respectively), utilizing DMSO-d6 as solvent and as an external reference. The following abbreviations are used for multiplicity of NMR signals: s—singlet, d—doublet, t—triplet, q—quartet, dd—doublet of doublets, dt–doublet of triplets, m—multiplet, br—broaded. Mass spectroscopy studies were performed on a Shimadzu GCMS-QP2010 Ultra (EI, 70 eV). IR spectra were recorded on a Bruker Alpha spectrometer equipped with a ZnSe ATR accessory. Elemental analysis was performed on a PerkinElmer PE 2400 elemental analyzer. Melting points were determined on a Stuart SMP3 and are uncorrected. The monitoring of the reaction progress was performed by using TLC on Silufol UV254 plates (eluent is AcOEt). All synthesized compounds are >95% pure by elemental analysis.
General procedure for the synthesis of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines (2a–k, 10a–k).
A suspension of 0.01 mol (1 equiv.) of the corresponding 6-cyano-7-aminoazolo[1,5-a]pyrimidine (1a-k, 9a-k) and 0.011 mol (1.1 equiv.) of sodium azide in 40 mL of DMF was stirred at 120 °C for 8 h under air atmosphere (TLC control, AcOEt as eluent, starting material Rf ≈ 0.6–0.7, tetrazole products Rf ≈ 0.0). The reaction mixture was cooled to 25 °C, evaporated at reduced pressure, residue was dissolved in 30 mL of H2O and acidified with conc. HCl to pH≈1. The obtained precipitate was filtered off and washed with 100 mL of H2O to give the corresponding product.
6-(1H-tetrazolTetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2a).
Brown solid. Yield 1.67 g, 83%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.58 (H, d, C3H, J = 2.2), 8.24 (H, d, C2H, J = 2.2), 8.70 (2H, s, NH2), 8.76 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 152.7, 148.4, 147.6, 146.0, 145.4, 96.4, 85.7. IR, ν, cm−1: 3259 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 77 (18), 105 (15), 145 (32), 159 (15), 174 (50), 202 (73), [M]+). Anal. Calcd. for C7H6N8: C 41.59, H 2.99, N 55.42; found: C 41.65, H 3.06, N 55.33.
2-methylMethyl-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2b).
Beige solid. Yield 1.84 g, 85%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.44 (3H, s, CH3), 6.39 (H, s, C3H), 8.61 (2H, s, NH2), 8.69 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 155.0, 152.6, 148.8, 147.3, 145.5, 96.0, 85.2, 14.4. IR, ν, cm−1: 3173 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 81 (19), 159 (28), 108 (50), 173 (18), 188 (53), 216 (85), [M]+). Anal. Calcd. for C8H8N8: C 44.44, H 3.73, N 51.83; found: C 44.39, H 3.76, N 51.83.
2-(methylthioMethylthio)-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2c).
Brown solid. Yield 1.95 g, 79%. Mp = 273–275 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.64 (3H, s, CH3), 6.41 (H, s, C3H), 8.56 (2H, s, NH2), 8.69 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.0, 152.4, 149.1, 147.8, 144.9, 94.5, 85.5, 13.9. IR, ν, cm−1: 3238 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (70), 131 (20), 159 (16), 173 (87), 220 (42), 248 (100), [M]+). Anal. Calcd. for C8H8N8S: C 38.70, H 3.25, N 45.14; found: C 38.79, H 3.11, N 45.23.
2-phenylPhenyl-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2d).
Yellow solid. Yield 2.64 g, 95%. Mp = 291–293 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.95 (H, s, C2H), 7.41 (H, t, C4’H, J = 7.6), 7.48 (2H, t, C3’H, C5’H, J = 7.6), 8.07 (2H, d, C2’H, C6’H, J = 7.6), 8.64 (2H, s, NH2), 8.76 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 155.6, 152.4, 149.1, 147.6, 145.9, 132.2, 129.3, 128.8, 126.4, 93.4, 85.9. IR, ν, cm−1: 3280 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (38), 77 (100), 116 (32), 170 (10), 208 (8), 221 (23), 250 (65), 278 (92), [M]+). Anal. Calcd. for C13H10N8: C 56.11, H 3.62, N 40.27; found: C 56.03, H 3.62, N 40.23.
2-(thiophenThiophen-2-yl)-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2e).
Brown solid. Yield 2.56 g, 90%. Mp = 297–298 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.83 (H, s, C3H), 7.15 (H, dd, C4’H, J1 = 5.0, J2 = 3.5), 7.54 (H, d, C3’H, J = 3.5), 7.68 (H, d, C5’H, J = 3.5), 8.56 (2H, s, NH2), 8.74 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 152.4, 151.3, 149.3, 148.0, 145.6, 135.2, 128.1, 127.5, 127.2, 93.3, 86.0. IR, ν, cm−1: 3348 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52(55), 93 (25), 148 (29), 227 (23), 241 (17), 256(70), 284 (100), [M]+). Anal. Calcd. for C11H8N8S: C 46.47, H 2.84, N 39.41; found: C 46.47, H 2.90, N 39.41.
3-carbonitrileCarbonitrile-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2f).
Brown solid. Yield 1.93 g, 82%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.64 (H, s, C2H), 8.83 (H, s, NH), 8.97 (H, s, C5H), 9.35 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 152.2, 150.7, 150.6, 147.6, 146.6, 113.5, 89.4, 80.8. IR, ν, cm−1: 2231 (CN); 3321 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 144 (92), 170 (18), 184 (15), 199 (52), 227 (63), [M]+). Anal. Calcd. for C8H5N9x1/2H2O: C 40.67, H 2.54, N 53.39; found: C 40.75, H 2.52, N 53.38.
3-ethoxycarbonylEthoxycarbonyl-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2g).
Beige solid. Yield 2.54 g, 90%. Mp = 288–290 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 1.36 (3H, t, CH3, J = 7.2), 4.30 (2H, q, CH2, J = 7.2), 8.44 (H, s, C2H), 8.70 (H, s, NH), 9.06 (H, s, C5H), 9.12 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 161.9, 153.8, 150.1, 147.5, 147.0, 146.0, 101.2, 91.1, 59.4, 14.5. IR, ν, cm−1: 1683 (COOEt); 3315 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 94 (70), 159 (100), 202 (46), 230 (27), 246 (11), 274 (50), [M]+). Anal. Calcd. for C10H10N8O2xH2O: C 41.10, H 4.11, N 38.36; found: C 41.00, H 4.15, N 38.37.
3-nitroNitro-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2h).
Yellow solid. Yield 1.48 g, 60%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.93 (H, s, C2H), 8.93 (H, s, NH), 9.08 (H, s, C5H), 9.52 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 152.4, 152.1, 146.6, 143.3, 142.9, 122.4, 91.6. IR, ν, cm−1: 1557 (NO2); 1267 (NO2); 3325 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 92 (18), 144 (14), 204 (5), 219 (63), 247 (50), [M]+). Anal. Calcd. for C7H5N9O2: C 34.01, H 2.04, N 51.00; found: C 33.98, H 1.89, N 51.13.
3-phenylPhenyl-6-(1H-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidin-7-amine (2i).
Yellow solid. Yield 1.92 g, 69%. Mp = 277–279 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.20 (H, t, C4’H, J = 7.8), 7.39 (2H, t, C3’H, C5’H, J = 7.8), 8.11 (2H, dd, C2’H, C6’H, J1 = 7.8, J2 = 1.2), 8.63 (H, s, C2H), 8.74 (2H, s, NH2), 8.85 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 152.40, 147.88, 146.17, 144.43, 143.39, 131.98, 128.59, 125.88, 125.60, 109.31, 86.07. IR, ν, cm−1: 3292 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (50), 142 (25), 235 (11), 250 (42), 278 (100), [M]+). Anal. Calcd. for C13H10N8: C 56.11, H 3.62, N 40.27; found: C 56.02, H 3.66, N 40.26.
2-(methylthioMethylthio)-3-ethoxycarbonlyl-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2j).
Yellow solid. Yield 2.91 g, 86%. Mp = 281–284 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 1.30 (3H, t, CH3, J = 7.2), 2.64 (3H, s, SCH3), 4.27 (2H, q, CH2, J = 7.2), 8.72 (2H, s, NH2), 8.84 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 162.0, 158.7, 152.2, 149.9, 148.9, 144.9, 98.8, 88.8, 59.5, 14.5, 12.8. IR, ν, cm−1: 1639 (COOEt); 3309 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 144 (23), 292 (30), 320 (83), [M]+). Anal. Calcd. for C11H12N8O2SxH2O: C 39.05, H 4.14, N 33.14; found: C 38.99, H 4.15, N 33.10.
2-(methylthioMethylthio)-3-carbonitrile-6-(1H-tetrazol-5-yl)-7-aminopyrazolo[1,5-a]pyrimidine (2k).
Orange solid. Yield 2.02 g, 74%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.75 (3H, s, CH3), 8.85 (H, s, NH), 8.90 (H, s, C5H), 9.01 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 157.4, 153.2, 151.4, 150.3, 145.3, 113.1, 91.6, 78.9, 13.2. IR, ν, cm−1: 2217 (CN); 3364 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 77 (37), 92 (49), 230 (31), 245 (43), 273 (52), [M]+). Anal. Calcd. for C9H7N9S: C 39.56, H 2.58, N 46.13; found: C 39.56, H 2.60, N 46.23.
6-(1H-tetrazolTetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10a).
Pale yellow solid. Yield 1.50 g, 74%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.47 (H, s, C2H), 8.82 (s, NH), 9.02 (H, s, C5H), 9.05 (s, NH). 13C NMR (150 MHz, DMSO-d6), δ, ppm.: 155.5, 155.4, 152.4, 146.8, 89.4. IR, ν, cm−1: 3322 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (98), 146 (32), 160 (10), 175 (100), 203 (60), [M]+). Anal. Calcd. for C6H5N9: C 35.47, H 2.48, N 62.05; found: C 35.55, H 2.38, N 62.01.
2-methylMethyl-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10b).
Beige solid. Yield 1.45 g, 64%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 3.08 (3H, s, CH3), 9.47 (2H, s, NH2), 9.54 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 164.5, 155.6, 153.7, 151.6, 145.9, 91.1, 14.8. IR, ν, cm−1: 3399 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (55), 83 (15), 174 (6), 189 (50), 217 (33), [M]+). Anal. Calcd. for C6H5N9x1/2H2O: C 37.17, H 3.54, N 55.75; found: C 37.17, H 3.55, N 55.71.
2-(methylthioMethylthio)-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10c).
Beige solid. Yield 1.94 g, 78%. Mp = 275–280 °C. 1H NMR (600 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.7 (3H, s, CH3), 8.7 (H, s, NH), 8.91 (H, s, C5H), 8.96 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 166.9, 155.7, 152.0, 152.0, 145.6, 89.2, 13.2. IR, ν, cm−1: 3404 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (95), 176 (20), 192 (8), 221 (66), 249 (100), [M]+). Anal. Calcd. for C7H7N9S: C 33.73, H 2.83, N 50.58; found: C 33.77, H 2.81, N 50.53.
2-(benzylthioBenzylthio)-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10d).
Yellow solid. Yield 2.76 g, 85%. Mp = 263–266 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 4.55 (2H, s, CH2), 7.25 (H, t, C4’H, J = 6.4), 7.32 (2H, t, C3’H, C5H, J = 6.4), 7.51 (2H, d, C2’H, C6’H, J = 7.2), 8.86 (2H, s, NH2), 8.90 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 165.9, 155.8, 152.4, 152.1, 145.7, 137.7, 129.0, 128.5, 127.3, 89.9, 34.6. IR, ν, cm−1: 3323 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (10), 91 (100), 282 (3), 325 (20), [M]+). Anal. Calcd. for C13H11N9S: C 47.99, H 3.41, N 38.75; found: C 47.98, H 3.40, N 38.83.
6-(1H-tetrazolTetrazol-5-yl)-2-(trifluoromethyl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10e).
Orange solid. Yield 1.14 g, 42%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.89 (H, s, NH), 9.12 (H, s, C5H), 9.67 (H, s, NH). 19F NMR (376 MHz, DMSO-d6), δ, ppm.: −64.96. 13C NMR (100 MHz, DMSO-d6), δ, ppm. (J, Hz): 155.9, 155.0, 154.0 (q, J = 38.6), 152.2, 147.5, 119.3 (q, J = 269.6), 91.1. IR, ν, cm−1: 3383 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (100), 69 (50), 214 (12), 243 (80), 271 (30), [M]+). Anal. Calcd. for C7H4F3N9S: C 31.01, H 1.49, N 21.02; found: C 30.90, H 1.33, N 21.19.
2-ethoxycarbonylEthoxycarbonyl-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10f).
Yellow solid. Yield 1.70 g, 58%. Mp = 226–228 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 1.44 (3H, t, CH3, J = 7.2), 4.46 (2H, q, CH2, J = 7.2), 8.86 (H, s, NH), 9.08 (H, s, C5H), 9.59 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 159.7, 156.2, 155.6, 153.5, 152.3, 147.2, 90.3, 61.8, 14.1. IR, ν, cm−1: 1650 (COOEt); 3255 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 160 (45), 232 (12), 247 (8), 275 (32), [M]+). Anal. Calcd. for C9H9N9O2xH2O: C 36.86, H 3.75, N 43.00; found: C 36.99, H 3.73, N 43.20.
2-phenylPhenyl-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10g).
Yellow solid. Yield 1.73 g, 62%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.5 (2H, d, J = 6.8, C3’ H, C5’H), 7.52 (H, s, C4’H), 8.26 (2H, dd, J1 = 7.6, J2 = 2.8, C2’H, C6’H), 8.88 (2H, s, NH2), 8.99 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 164.1, 156.1, 152.4, 152.2, 146.6, 130.6, 130.3, 128.9, 126.9, 89.2. IR, ν, cm−1: 3361 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (39), 77 (65), 251 (55), 279 (32), [M]+). Anal. Calcd. for C12H9N9: C 51.61, H 3.25, N 45.14; found: C 51.61, H 3.23, N 45.28.
2-(furanFuran-2-yl)-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10h).
Beige solid. Yield 1.67 g, 60%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.65 (H, dd, C4’H, J = 2.4), 7.18 (H, d, C3’H, J = 3.2), 7.82 (H, s, C5’H), 8.99 (2H, s, NH2), 9.04 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 157.1, 155.8, 152.6, 152.2, 146.6, 145.6, 145.3, 112.56, 112.2, 89.5. IR, ν, cm−1: 3255 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (41), 94 (100), 160 (23), 212 (20), 226 (18), 241(65), 269 (65), [M]+). Anal. Calcd. for C10H7N9O2x1/2H2O: C 43.16, H 2.88, N 45.32; found: C 43.15, H 2.92, N 45.31.
2-(thiophenThiophen-2-yl)-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10i).
Beige solid. Yield 2.39 g, 83%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.24 (H, t, C4’H, J = 4.4), 7.78 (H, d, C3’H, J = 4.8), 7.86 (H, d, C5’H, J = 3.6), 8.89 (2H, s, NH2), 8.92 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm 160.4, 155.9, 152.5, 152.2, 146.4, 133.0, 129.5, 128.4, 128.3, 89.5. IR, ν, cm−1: 3250 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (53), 110 (100), 228 (15), 242 (33), 257 (48), 285 (52), [M]+). Anal. Calcd. for C10H7N9S: C 42.10, H 2.47, N 44.19; found: C 42.01, H 2.55, N 44.20.
2-(pyridinPyridin-3-yl)-6-(1H-tetrazol-5-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidine (10j).
Beige solid. Yield 2.49 g, 83%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.56 (H, t, C5’H, J = 6.4), 8.55 (H, d, C6’H, J = 7.6), 8.69 (H, s, C4’H), 8.96 (2H, s, NH2), 9.03 (H, s, C5H), 9.41 (H, s, C2’H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 161.9, 156.0, 152.6, 152.3, 150.9, 147.5, 146.5, 134.3, 126.2, 123.9, 89.6. IR, υ, cm−1: 3240 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (63), 105 (100), 223 (12), 237 (74), 252 (53), 280 (35), [M]+). Anal. Calcd. for C11H8N10: C 47.14, H 2.88, N 49.98; found: C 47.16, H 2.87, N 50.00.
6-(1H-tetrazolTetrazol-5-yl)-2,7-diamino-[1,2,4]triazolo[1,5-a]pyrimidine (10k).
Yellow solid. Yield 1.44 g, 66%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.10 (2H, s, C2-NH2), 8.34 (2H, s, C7-NH2), 8.72 (H, s, C5H). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 166.5, 155.3, 152.3, 150.3, 144.7, 88.6. IR, ν, cm−1: 3331 (NH2); 3425 (NH2). MS (EI, 70 eV), m/z, (Irel), %: 52 (35), 120 (40), 161 (7), 175 (13), 190 (21), 218 (18), [M]+). Anal. Calcd. for C6H6N10: C 33.03, H 2.77, N 64.20; found: C 32.90, H 2.77, N 64.38.
General procedure for the synthesis of sodium 5-(7-aminoazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ides (3,11).
A suspension of 0.005 mol (1 equiv.) of the corresponding 6-(tetrazol-5-yl)azolo[1,5-a]pyrimidin-7-amines and 0.005 mol (0.42 g, 1 equiv.) of sodium bicarbonate in 30 mL of deionized H2O was refluxed for 5 min under air atmosphere. The resulting solution was cooled to 25 °C, evaporated at reduced pressure to dryness to give the corresponding product.
Sodium 5-(7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3a).
Beige solid. Yield 1.19 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.34 (H, d, J = 2.0, C3H), 7.76 (H, s, NH), 7.98 (H, d, J = 2.0, C2H), 8.91 (H, s, C5H), 9.20 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 157.2, 148.3, 147.8, 144.9, 144.1, 94.7, 92.5. IR, ν, cm–1: 3333 (NH2). Anal. Calcd. for C7H5N8NaxH2O: C 34.72, H 2.91, N 46.27, found: C 34.72, H 3.00, N 46.39.
Sodium 5-(2-methyl-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3b).
Brown solid. Yield 1.21 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.44 (3H, s, CH3), 6.11 (H, s, C3H), 7.52 (H, s, NH), 8.85 (H, s, C5H), 9.13 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 157.3, 153.3, 148.9, 147.4, 144.4, 94.1, 92.3, 14.4. IR, ν, cm–1: 3397 (NH2). Anal. Calcd. for C8H7N8NaxH2O: C 37.50, H 3.54, N 43.74, found: C 37.55, H 3.59, N 43.66.
Sodium 5-(2-(methylthio)-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3c).
Brown solid. Yield 1.38 g, 96%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.62 (3H, s, CH3), 6.24 (H, s, C3H), 7.68 (H, s, NH), 8.84 (H, s, C5H), 9.20 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 157.1, 154.0, 149.1, 147.7, 144.0, 92.8, 92.7, 14.1. IR, ν, cm–1: 3397 (NH2). Anal. Calcd. for C8H7N8NaSxH2O: C 33.33, H 3.15, N 38.87, found: C 33.21, H 3.10, N 38.86.
Sodium 5-(3-cyano-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3f).
Brown solid. Yield 1.32 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.44 (H, s, C3H), 8.44 (H, s, NH), 9.08 (H, s, C5H), 9.64 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.25, 149.81, 149.78, 147.02, 145.81, 114.33, 96.28, 78.88. IR, ν, cm–1: 2241 (CN). Anal. Calcd. for C8H4N9NaxH2O: C 35.96, H 2.26, N 47.18, found: C 36.02, H 2.26, N 47.11.
Sodium 5-(3-(ethoxycarbonyl)-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3g).
Beige solid. Yield 1.55 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 1.32 (3H, t, J = 7.2, CH3), 4.28 (2H, q, J = 7.2, CH2), 8.52 (H, s, C2H), 8.53 (H, s, NH), 9.10 (H, s, C5H), 9.47 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 162.26, 156.43, 149.68, 147.20, 146.58, 145.42, 100.14, 95.67, 59.19, 14.53. IR, ν, cm−1: 1608 (COOEt), 3326 (NH2). Anal. Calcd. for C10H9N8NaO2xH2O: C 38.22, H 3.53, N 35.66, found: C 38.20, H 3.57, N 35.66.
Sodium 5-(3-nitro-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3h).
Yellow solid. Yield 1.51 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.95 (H, s, C2H), 9.01 (H, s, NH), 9.18 (H, s, C5H), 9.76 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.0, 150.9, 145.9, 142.6, 142.5, 121.5, 98.5. IR, ν, cm−1: 1373 (NO2), 1645 (NO2), 3316 (NH2). Anal. Calcd. for C7H4N9NaO2x2H2O: C 27.55, H 2.64, N 41.31, found: C 27.69, H 2.75, N 41.49.
Sodium 5-(3-phenyl-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3i).
Yellow solid. Yield 1.42 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.15 (H, t, C4’H, J = 7.6), 7.37 (2H, t, C3’H, C5’H, J = 7.6), 7.90 (H, s, NH), 8.14 (2H, d, C2’H, C6’H, J = 7.6), 8.47 (H, s, C2H), 9.02 (H, s, C5H), 9.32 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.94, 147.89, 145.03, 144.95, 144.47, 141.92, 132.89, 128.52, 125.23, 125.20, 107.53, 93.34, 93.30. IR, ν, cm−1: 3366 (NH2). Anal. Calcd. for C13H9N8Na: C 52.00, H 3.02, N 37.32, found: C 52.03, H 2.99, N 37.20.
Sodium 5-(2-(methylthio)-3-(ethoxycarbonyl)-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3j).
Beige solid. Yield 1.78 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 1.40 (3H, t, CH3, J = 7.2), 2.63 (3H, s, CH3), 4.31 (2H, q, CH2, J = 7.2), 7.99 (H, s, NH2), 9.07 (H, s, C5H), 9.50 (H, s, NH2). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 162.5, 157.7, 156.4, 149.2, 148.4, 144.3, 97.1, 95.9, 59.2, 14.6, 12.7. IR, ν, cm−1: 1670 (COOEt). Anal. Calcd. for C11H11N8NaO2SxH2O: C 36.67, H 3.64, N 31.10, found: C 36.67, H 3.69, N 30.95.
Sodium 5-(2-(methyilthio)-3-cyano-7-aminopyrazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (3k).
Orange solid. Yield 1.55 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.75 (3H, s, CH3), 8.62 (H, s, NH), 8.98 (H, s, CH), 9.58 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.8, 156.2, 150.9, 149.5, 145.0, 113.7, 96.6, 77.7, 13.3. IR, ν, cm−1: 2224 (CN), 3382 (NH2). Anal. Calcd. for C9H6N9NaSxH2O: C 34.51, H 2.57, N 40.24, found: C 34.39, H 2.60, N 40.07.
Sodium 5-(7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11a).
Yellow solid. Yield 1.16 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.49 (H, s, C2H), 8.60 (H, s, NH), 9.13 (H, s, C5H), 9.44 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.4, 154.8, 151.3, 145.9, 95.7. IR, ν, cm−1: 3342 (NH2). Anal. Calcd. for C6H4N9NaxH2O: C 29.64, H 2.49, N 51.84, found: C 29.66, H 2.51, N 51.96.
Sodium 5-(2-methyl-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11b).
Beige solid. Yield 1.22 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.48 (3H, s, CH3), 8.35 (H, s, NH), 9.01 (H, s, C5H), 9.36 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 163.9, 156.5, 155.3, 150.8, 145.4, 95.5, 14.8. IR, ν, cm−1: 3364 (NH2). Anal. Calcd. for C7H6N9NaxH2O: C 32.69, H 3.14, N 49.01, found: C 32.70, H 3.01, N 49.15.
Sodium 5-(2-(methylthio)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11c).
Orange solid. Yield 1.43 g, 99%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 2.68 (3H, s, CH3), 8.36 (H, s, NH), 9.00 (H, s, C5H), 9.40 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 165.9, 156.3, 155.3, 150.6, 144.9, 96.0, 13.4. IR, ν, cm−1: 3376 (NH2). Anal. Calcd. for C7H6N9NaSxH2O: C 29.07, H 2.79, N 43.58, found: C 29.09, H 2.66, N 43.63.
Sodium 5-(2-(benzylthio)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11d).
Pale yellow solid. Yield 1.65 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 4.52 (2H, s, CH2), 7.22 (H, t, C4’H, J = 7.2), 7.29 (2H, t, C3’H, C5’H, J = 7.2), 7.48 (2H, d, C2’H, C6’H, J = 7.2), 8.23 (H, s, NH), 9.04 (H, s, C5H), 9.43 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 164.8, 156.3, 155.1, 150.6, 144.9, 137.9, 129.0, 128.5, 127.3, 96.2, 34.5. IR, ν, cm−1: 3363 (NH2). Anal. Calcd. for C13H10N9NaS: C 44.95, H 2.90, N 36.29, found: C 45.01, H 3.05, N 36.27.
Sodium 5-(2-(trifluoromethyl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11e).
Orange solid. Yield 1.45 g, 93%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 8.88 (H, s, NH), 9.22 (H, s, C5H), 9.71 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm, (J, Hz): 156.1, 155.0, 154.5 (q, J = 38.6), 152.5, 146.4, 119.6 (q, J = 269.6), 97.6. IR, ν, cm−1: 3242 (NH2). Anal. Calcd. for C7H3F3N9NaxH2O: C 27.02, H 1.62, N 40.51, found: C 26.91, H 1.68, N 40.34.
Sodium 5-(2-phenyl-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11g).
Yellow solid. Yield 1.43 g, 95%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.50 (H, m, C4’H), 7.52 (2H, m, C3’H, C5’H), 8.21 (H, s, NH), 8.26 (2H, d, C2’H, C6’H, J = 6.8), 9.10 (H, s, C5H), 9.49 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 163.5, 156.5, 155.6, 151.4, 145.7, 130.9, 130.3, 128.9, 126.9, 96.1. IR, ν, cm−1: 3258 (NH2). Anal. Calcd. for C12H8N9Na: C 47.84, H 2.68, N 41.85, found: C 47.84, H 2.66, N 41.90.
Sodium 5-(2-(furan-2-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11h).
Orange solid. Yield 1.48 g, 96%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 6.65 (H, dd, C4’H, J1 = 2.0, J2 = 1.6), 7.15 (H, d, C3’H, J = 2.8), 7.80 (H, s, C5’H), 8.47 (H, s, NH), 9.10 (H, s, C5H), 9.50 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 156.7, 156.4, 155.2, 151.4, 146.2, 145.7, 144.9, 112.1, 111.8, 96.2. IR, ν, cm−1: 3228 (NH2). Anal. Calcd. for C10H6N9NaxH2O: C 38.84, H 2.61, N 40.77, found: C 38.90, H 2.66, N 40.59.
Sodium 5-(2-(pyridin-3-yl)-7-amino-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)tetrazol-1-ide (11j).
Pale yellow solid. Yield 1.49 g, 93%. Mp > 300 °C. 1H NMR (400 MHz, DMSO-d6), δ, ppm. (J, Hz): 7.53 (H, dd, C5’H, J1 = 8.0, J2 = 3.2), 8.37 (H, s, NH), 8.54 (H, dt, C4’H, J1 = 8.0, J2 = 1.6), 8.66 (H, dd, C6’H, J1 = 3.2, J2 = 1.6), 9.13 (H, s, C5H), 9.40 (H, d, C2’H, J = 2.4), 9.54 (H, s, NH). 13C NMR (100 MHz, DMSO-d6), δ, ppm.: 161.8, 156.8, 156.0, 151.9, 151.5, 148.3, 146.2, 134.6, 127.3, 124.5, 96.8. IR, ν, cm−1: 3348 (NH2). Anal. Calcd. for C11H7N10NaxH2O: C 41.26, H 2.83, N 43.74, found: C 41.21, H 2.71, N 43.88.