3-AMINO-4,5,6,7-TETRAHYDRO-BENZO[B]THIOPHENE-2-CARBOXYLIC ACID METHYL ESTER

Methyl-S-(2-cyanocyclohex-1-enyl)sulphanylacetate (9) (0.17 g, 0.78 mmol) was mixed with freshly distilled dry THF (3 mL). Potassium t-butoxide (0.09 g, 0.78 mmol) was added and the solution was heated at reflux for 30 minutes. The reaction was monitored by TLC (eluent: PE/EtOAc 5:1). The mixture was concentrated under vacuum, CHCompound B1 (5.00 g, 23.7 mmol, 1 equiv) was dissolved in distilled CH2Cl2 (50 mL) and then TsCl (6.77 g, 35.5 mmol, 1.5 equiv) and pyridine (2.81 g, 35.5 mmol, 1.5 equiv) were added. The mixture was stirred for 22 h at r.t. under argon. The starting ester was still detectedby TLC (CH2Cl2) and therefore extra TsCl (4.51 g, 23.7 mmol, 1 equiv)and pyridine (1.87 g, 23.7 mmol, 1 equiv) were added and the mixturewas stirred for a further 21 h. H2O (35 mL) was then added and the mixture was stirred for 2 h. The organic phase was separated, and the aqueous phase was washed with CH2Cl2 (3 × 10 mL). The combined organic phases were dried (MgSO4) and concentrated. The crude brown solid was recrystallized (EtOH) to give a colorless solid; yield: 5.80 g (67%); mp 114-116 C. IR (KBr): 1057, 1095, 1163, 1186, 1198, 1284, 1323, 1396, 1446, 1475, 1560, 1595, 1680, 2931, 2953, 3153, 3190, 3207 cm-1. 1H NMR (300 MHz, CDCl3): delta = 1.74-1.77 and 1.86-1.90 (m, 4 H, H5 +H6), 2.39 (s, 3 H, C6H4CH3), 2.74-2.83 (m, 4 H, H4 + H7), 3.54 (s, 3 H, COOCH3), 7.19 (d, J = 7.5 Hz, 2 H, C6H4CH3), 7.53 (d, J = 7.5 Hz, 2 H, C6H4CH3), 8.17 (br s, 1 H, NH). 13C NMR (75 MHz, CDCl3): delta = 21.6 (C6H4CH3), 22.3 and 22.9 (CH2-C5 +C6), 24.9 (CH2-C4), 26.0 (CH2-C7), 51.7 (COOCH3), 116.8 (C), 127.6 and 129.1 (2 × 2CH-C6H4CH3), 135.1 (C), 135.4 (C), 140.6 (C), 143.5 (C), 143.9 (C), 163.1 (COOCH3). MS (EI, 70 eV): m/z (%) = 365 [M+] (10), 210 (100), 196 (10), 178 (20), 154 (10), 91 (15), 65 (10).Methyl-S-(2-cyanocyclohex-1-enyl)sulphanylacetate (9) (0.17 g, 0.78 mmol) was mixed with freshly distilled dry THF (3 mL). Potassium t-butoxide (0.09 g, 0.78 mmol) was added and the solution was heated at reflux for 30 minutes. The reaction was monitored by TLC (eluent: PE/EtOAc 5:1). The mixture was concentrated under vacuum, CH2Cl2 (25 mL) was added and the solution was washed by distilled water (2x20 mL) and dried over MgSO4. The solvent was evaporated and the obtained oil was dried under high vacuum (10-1 mbar). The yellowish solid was obtained after refrigerating overnight (135 mg, 80 %). Mp 70-73 C; deltaH (CDCl3): 1.82 (m, 4H, H5 a H6), 2.30 (m, 2H, H7), 2.67 (m, 2H, H4), 3.79 (s, 3H, COOCH3), 5.36 (brs, 2H, NH2); deltaC (CDCl3): 21.9 and 22.6 (2CH2 - C5 and C6), 23.1 (CH2 - C4), 25.8 (CH2 - C7), 51.1 (COOCH3), 97.3 (CAr), 126.2 (CAr), 143.5 (CAr), 152.6 (CAr), 165.4 (COOCH3); IR (KBr): 768, 1072, 1095, 1130, 1198, 1263, 1300, 1342, 1448, 1493, 1568, 1604, 1668, 1734 (ester), 2858, 2933, 3361 (NH2), 3464 (NH2); MS (EI, 70 eV): m/z (%) = 32 (80), 40 (10), 45 (10), 65 (10), 77 (15), 91 (15), 118 (15), 151 (65), 179 (90), 211 (M+, 100), 212 (M+H+, 10); HRMS-FAB: m/z [M+H]+ calcd for C10H13NO2S: 211.0667; found: 211.0745.

Molecular Weight:211.28
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:211.06669983
Monoisotopic Mass:211.06669983
Topological Polar Surface Area:80.6
Heavy Atom Count:14
Complexity:234
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes