Arkivoc 2019, iv, 0-0
Mabank, T. et al.
(morpholine-2xOCH2), 113.0 (ArCH), 113.7 (ArCH), 124.4 (ArCH), 127.4 (ArC), 134.6 (ArC), 158.5 (C-O). HRMS
ESI+ calcd for C14H21N2O4S [M+H]+, 313.1222, found, 313.1218.
6-Hydroxy-N-(4’-hydroxyphenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29c) was obtained via
1
demethylation Method B from 28c, as a thick white oil (62 mg, 32%), Rf 0.24 (50:50 EtOAc/Hexane). H NMR
(300 MHz, CD3OD): δH 7.09–6.97 (m, 2H, ArH and NH), 6.85 (d, J 8.3 Hz, 1H, ArH), 6.77–6.54 (m, 3H, ArH), 6.50
(d, J 6.5 Hz, 2H, ArH), 4.59 (brs, 1H, OH), 4.26 (s, 2H, ArCH2N), 3.38 (t, J 5.9 Hz, 2H, NCH2), 2.65 (t, J 5.9 Hz, 2H,
ArCH2CH2). 13C NMR (75 MHz, CD3OD): δC 20.7 (ArCH2CH2), 36.1 (NCH2), 39.1 (ArCH2N), 105.6 (ArCH), 106.7
(ArCH), 107.3 (ArC), 115.2 (ArCH), 115.3 (ArCH), 116.2 (ArCH), 119.0 (ArCH), 121.3 (ArCH), 121.5 (ArC), 126.8
(ArCNH), 146.8 (C-O), 147.7 (C-O). HRMS ESI+ calcd for C15H16N2O4S [M+H]+, 321.0864, found, 321.0912.
N-(3’-Chlorophenyl)-6-hydroxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29d) was obtained via demethyl-
1
ation Method A from 28c, as a colourless oil (77 mg, 34%), Rf 0.41 (50:50 EtOAc/Hexane). H NMR (300 MHz,
CDCl3): δH 7.28–7.24 (m, 1H, NH), 7.18 (d, J 8.0 Hz, 1H, ArH), 7.13–6.96 (m, 2H, ArH), 6.90 (d, J 8.3 Hz, 1H, ArH),
6.71–6.51 (m, 2H, ArH), 4.71 (brs, 1H, OH), 4.41 (s, 2H, ArCH2N), 3.55 (t, J 6.0 Hz, 2H, NCH2), 2.77 (t, J 6.0 Hz,
2H, ArCH2CH2). 13C NMR (75 MHz, CDCl3): δC 29.0 (ArCH2CH2), 44.4 (CH2), 47.5 (ArCH2N), 114.3 (ArCH), 115.5
(ArCH), 118.4 (ArCH), 120.4 (ArCH), 121.3 (ArC), 124.1 (ArCH), 125.0 (ArCH), 127.8 (ArCH), 130.6 (ArCCl), 135.0
(ArC), 135.3 (ArCNH), 154.6 (C-O). HRMS ESI+ calcd for C15H16ClN2O3S [M+H]+, 339.0571 (35Cl), found 339.0570.
N-(3’-Fluorophenyl)-6-hydroxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29e) was obtained via
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demethylation Method A from 28e, as a brown oil (22 mg, 10%), Rf 0.32 (50:50 EtOAc/Hexane). H NMR (300
MHz, CDCl3): δH 7.38–7.08 (m, 2H, ArH and NH), 7.01–6.44 (m, 6H, ArH), 4.87 (s, 1H, OH), 4.41 (d, J 6.0 Hz, 2H,
ArCH2N), 3.54 (t, J 6.0 Hz, 2H, NCH2), 2.77 (t, J 6.0 Hz, 2H, ArCH2CH2). 13C NMR (75 MHz, CDCl3): δC 29.0
(ArCH2CH2), 44.4 (CH2), 47.6 (ArCH2N), 107.6 (d, J 25.5 Hz, ArCH-F), 111.7 (d, J 30.75 Hz, ArCH-F), 114.3 (ArCH),
115.5 (ArCH), 115.6 (ArCH), 115.6 (ArC), 124.1 (ArCH), 127.8 (ArCH), 130.8 (ArCH), 130.9 (ArC), 135.0 (ArCH),
148.6 (ArCNH), 154.6 (C-O). HRMS ESI+ calcd for C15H16FN2O3S [M+H]+, 323.0866, found, 323.0854.
N-(4’-Chlorophenyl)-6-hydroxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29f) was obtained via demethyl-
1
ation Method A from 28f, as a colourless oil (94 mg, 41%), Rf 0.41 (50:50 EtOAc/Hexane). H NMR (300 MHz,
CDCl3): δH 7.27–7.21 (m, 3H, ArH and NH), 7.09–7.06 (m, 2H, ArH), 6.90–6.56 (m, 3H, ArH), 4.39 (s, 2H,
ArCH2N), 3.71–3.35 (m, 2H, NCH2), 2.76 (m, 2H, ArCH2CH2). 13C NMR (75 MHz, CDCl3, overlapping signals): δC
29.0 (ArCH2CH2), 44.4 (CH2), 47.5 (ArCH2N), 114.3 (ArCH), 115.4 (ArCH), 122.2 (ArC), 127.8 (ArCH), 129.7
(ArCH), 130.4 (ArC), 134.8 (ArCCl), 135.8 (ArCNH), 154.6 (C-O). HRMS ESI+ calcd for C15H16ClN2O3S [M+H]+,
339.0571 (35Cl), found 339.0556.
N-(4’-Fluorophenyl)-6-hydroxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29g) was obtained via demethyl-
1
ation Method A from 28g, as a brown oil (71.0 mg, 33%), Rf 0.32 (50:50 EtOAc/Hexane). H NMR (300 MHz,
CDCl3): δH 7.12–7.06 (m, 2H, ArH), 7.96–6.83 (m, 6H, ArH and NH), 4.36 (d, J 10.3 Hz, 2H, ArCH2N), 3.51–3.47
(m, 2H, NCH2), 2.71 (t, J 6.0 Hz, 2H, ArCH2CH2). 13C NMR (75 MHz, CDCl3): δC 29.8 (ArCH2CH2), 44.0 (CH2), 47.3
(ArCH2N), 112.9 (ArCH), 114.2 (ArCH), 116.0 (ArC), 116.3 (ArCH), 123.5 (d, J 8.2 Hz, ArCH-F), 125.7 (ArC), 126.6
(ArCH), 133.5 (ArCNH), 151.3 (ArC-F), 161.8 (C-O). HRMS ESI+ calcd for C15H16FN2O3S [M+H]+, 323.0866, found,
323.0858.
2-(Morpholinosulfonyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (29h) was obtained via demethylation Method B
from 28h as a white solid (45.0 mg, 25%), mp 168–170 oC, Rf 0.53 (100% EtOAc). 1H NMR (300 MHz,CD3OD): δC
6.94 (d, J 8.2 Hz, 1H, ArH), 6.72–6.51 (m, 2H, ArH), 4.37 (s, 2H, ArCH2N), 3.69 (sharp m, 4H, morpholine-
2xCH2O), 3.54 (t, J 5.5 Hz, 2H, NCH2), 3.22–3.18 (m, 4H, morpholine-2xNCH2), 2.86 (t, J 5.5 Hz, 2H, ArCH2CH2).
13C NMR (75 MHz, CD3OD): δC 29.9 (ArCH2CH2), 45.3 (morpholine-2xNCH2), 47.7 (CH2), 48.6 (ArCH2N), 67.4
(morpholine-2xCH2O), 114.9 (ArCH), 116.0 (ArCH), 124.6 (ArC), 128.3 (ArCH), 135.9 (ArC), 157.1 (C-O). HRMS
ESI+ calcd for C13H19N2O4S [M+H]+, 299.1066, found, 299.1055.
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