Development of Novel Anti-HIV Pyrimidobenzothiazine Derivatives by Tsukasa Mizuhara

Author:Tsukasa Mizuhara
Language: eng
Format: epub
Publisher: Springer Japan, Tokyo

3.1.30 Synthesis of 3,4-Dihydro-10-vinyl-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (26m)

N -( tert -Butyl)-3,4-dihydro-10-vinyl-2 H, 6 H -pyrimido[1,2- c ][1,3]benzothiazin-6-imine (23m). Using the general procedure as described for 22l, 10-bromo-N-(tert-butyl)-3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine 23k (52.8 mg, 0.15 mmol) was allowed to react with vinylboronic acid pinacol ester (0.031 mL, 0.18 mmol) for 1 h. Purification by flash chromatography over aluminum oxide with n-hexane–EtOAc (1:0 to 9:1) gave the title compound 23m as a colorless oil (30.5 mg, 68 %): IR (neat) cm−1: 1595 (C=N); 1H-NMR (400 MHz, CDCl3) δ: 1.38 (9H, s, 3 × CH3), 1.89–1.94 (2H, m, CH2), 3.63 (2H, t, J = 5.4 Hz, CH2), 3.87 (2H, t, J = 6.0 Hz, CH2), 5.24 (1H, d, J = 11.0 Hz, CH), 5.77 (1H, d, J = 17.6 Hz, CH), 6.69 (1H, dd, J = 17.6, 11.0 Hz, CH), 7.07 (1H, d, J = 8.3 Hz, Ar), 7.40 (1H, dd, J = 8.3, 2.0 Hz, Ar), 8.20 (1H, d, J = 2.0 Hz, Ar); 13C-NMR (100 MHz, CDCl3) δ: 21.9, 30.0 (3C), 45.1, 45.4, 54.1, 114.1, 124.7, 126.6, 127.4, 127.8, 128.2, 135.7, 135.9, 138.2, 147.9; HRMS (FAB): m/z calcd for C17H22N3S [M + H]+ 300.1534; found: 300.1532.

Compound 26m. Using the general procedure as described for 25a, compound 23m (7.3 mg, 0.024 mmol) was allowed to react for 1 h with TFA (1.0 mL) and MS4Å (150 mg). Purification by flash chromatography over aluminum oxide with n-hexane–EtOAc (9:1) gave the title compound 26m as colorless solid (3.7 mg, 62 %): mp 69–70 °C (from CHCl3–n-hexane); IR (neat) cm−1: 1622 (C=N), 1550 (C=N); 1H-NMR (400 MHz, CDCl3) δ: 1.95-2.01 (2H, m, CH2), 3.70 (2H, t, J = 5.7 Hz, CH2), 4.02 (2H, t, J = 6.2 Hz, CH2), 5.27 (1H, dd, J = 10.7, 0.6 Hz, CH), 5.79 (1H, dd, J = 17.7, 0.6 Hz, CH), 6.69 (1H, dd, J = 17.7, 10.7 Hz, CH), 7.00 (1H, d, J = 8.3 Hz, Ar), 7.19 (1H, br s, NH), 7.42 (1H, dd, J = 8.3, 2.0 Hz, Ar), 8.23 (1H, d, J = 2.0 Hz, Ar); 13C-NMR (100 MHz, CDCl3) δ: 21.0, 43.8, 44.9, 114.5, 123.8, 126.8, 126.9, 127.8, 127.9, 135.6, 135.9, 146.5, 153.2; HRMS (FAB): m/z calcd for C13H14N3S [M + H]+ 244.0908; found: 244.0902.

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