Full Papers
doi.org/10.1002/ejoc.202100593
1
solid. Rf =0.29 (EtOAc). H-NMR (500 MHz, DMSO-d6): δ=12.59 (s,
1H, NHCO), 9.27 (s, 1H, CHarom), 8.68 (s, 1H, NH), 8.51 (s, 1H, CHarom),
8.11 (s, 1H, CHarom), 7.13 (s, 1H, CHarom), 2.71 (s, 3H, CH3), 2.64 (s, 3H,
SCH3), 2.50 (s, 3H, SCH3) ppm. 13C-NMR (126 MHz, DMSO-d6): δ=
168.2 (1 C, CaromSCH3), 164.1 (1 C, CaromSCH3), 159.3 (1 C, CHarom),
156.4 (1 C, NHCO), 155.6 (1 C, Carom), 147.0 (1 C, Carom), 144.6 (1 C,
7-((tert-Butoxycarbonyl)(6-methyl-2-(methylthio)pyrido[3,2-d]
pyrimidin-7-yl)amino)-2-(methylthio)pyrido[3,2-d]
pyrimidin-6-yl 4-methylbenzenesulfonate (30a)
C
arom), 143.6 (1 C, CHarom), 140.3 (1 C, Carom), 139.5 (1 C, Carom), 133.8
(1 C, Carom), 123.5 (1 C, Carom), 121.9 (1 C, CHarom), 106.8 (1 C, CHarom),
21.5 (1 C, CH3), 14.0 (1 C, SCH3), 13.7 (1 C, SCH3) ppm. FT-IR: neat;
~
v=3264 (w), 3144 (w), 2840 (w), 2740 (w), 2192 (w), 1679 (m), 1617
(w), 1599 (w), 1576 (w), 1536 (s), 1444 (w), 1421 (w), 1398 (w), 1371
(m), 1334 (w), 1312 (w), 1223 (w), 1179 (w), 1132 (m), 963 (w), 940
(w), 851 (w), 760 (w), 708 (w), 690 (w), 656 (w), 636 (w), 604 (w), 582
Compound 29 (100 mg, 201 μmol, 1.00 eq), TosCl (46.0 mg,
241 μmol, 1.20 eq) and DMAP (2.5 mg, 20 μmol, 0.10 eq) were
°
suspended in THF (3.50 mL) cooled to 0 C and DIPEA (41.0 μL,
(m), 533 (w), 514 (w), 448 (w), 417 (w) cm-1. m.p.: 285 C
°
241 μmol, 1.20 eq) was added. The solution was stirred for 6 h
before it was poured into saturated aqueous NH4Cl-solution (10
mL) and extracted with EtOAc (3×20 mL). The combined organic
layers were washed with brine (20 mL), dried over Na2SO4 and the
solvent was evaporated under reduced pressure. The crude product
was purified by column chromatography on silica (n-pentane/EtOAc
2:1) to give as single regioisomer compound 30a (124 mg,
190 μmol, 95%, 99% brsm) as pale yellow foam. Rf =0.39 (n-
pentane/EtOAc 2:1). 1H-NMR (500 MHz, CDCl3): δ=9.38 (s, 1H,
CHarom), 9.08 (s, 1H, CHarom), 7.95 (s, 1H, CHarom), 7.93 (d, J=8.3 Hz,
2H, 2×CHTos), 7.85 (s, 1H, CHarom), 7.31 (d, J=8.3 Hz, 2H, 2×CHTos),
2.78 (s, 3H, CH3), 2.63 (s, 3H, SCH3), 2.61 (s, 3H, SCH3), 2.45 (s, 3H,
Tos-CH3) ppm. 13C-NMR (126 MHz, CDCl3): δ=171.1 (1 C, CaromSCH3),
170.3 (1 C, CaromSCH3), 159.9 (1 C, CHarom), 159.1 (1 C, CHarom), 159.0
decomposition (MeOH). HRMS (ESI+): m/z calc. for C17H15N7O1S2H1
[M+H]+: 398.0852, found: 398.0850.
tert-Butyl (6-methyl-2-(methylthio)pyrido[3,2-d]
pyrimidin-7-yl)(2-(methylthio)-6-oxo-5,6-dihydropyrido[3,2-d]
pyrimidin-7-yl)carbamate (29)
t
(1 C, Carom), 151.6 (1 C, NCO2 Bu), 151.0 (1 C, Carom), 146.6 (1 C, Carom),
Compound 28b (100 mg, 252 μmol, 1.00 eq) and DMAP (3.1 mg,
146.4 (1 C, Carom) 146.4 (1 C, CTos), 141.7 (1 C, Carom), 136.0 (1 C, Carom),
135.1 (1 C, CHarom), 134.2 (1 C, Carom), 133.5 (1 C, Carom), 133.5 (1 C,
°
25 μmol, 0.10 eq) were suspended in THF (4.50 mL) cooled to 0 C
and DIPEA (90 μL, 528 μmol, 2.10 eq) was added. The solution was
stirred for 5 min before Boc2O (1 m in THF, 516 μL, 516 μmol,
2.05 eq) was added. The reaction mixture was stirred for 5.5 h while
it was allowed to warm to rt. The dark orange reaction mixture was
poured into saturated aqueous NH4Cl-solution (10 mL) and
extracted with EtOAc (3×20 mL). The combined organic layers
were washed with brine (20 mL), dried over Na2SO4 and the solvent
was evaporated under reduced pressure. The crude product was
purified by column chromatography on silica (n-pentane/EtOAc 2:1
to EtOAc) to give as single regioisomer Boc2-compound (71.0 mg,
119 μmol, 47%, 51% brsm) as white foam and Boc1-compound 29
(55.0 mg, 111 μmol, 44%, 48% brsm) as pale yellow solid. By doing
2D-TLC it was found that Boc2-compound decomposes during
column chromatography on silica to Boc1-compound 29 with the
free amide-functionality. That’s why Boc2-compound was later on
converted into Boc1-compound 29 by doing another column. The
overall yield is 91% and 99% brsm respectively. Rf =0.81 (EtOAc).
1H-NMR (500 MHz, DMSO-d6): δ=12.44 (s, 1H, NHCO), 9.35 (s, 1H,
CHarom), 8.70 (s, 1H, CHarom), 8.05 (s, 1H, CHarom), 8.04 (s, 1H, CHarom),
2.71 (s, 3H, CH3), 2.57 (s, 3H, SCH3), 2.53 (s, 3H, SCH3), 1.42 (s, 9H,
C(CH3)3) ppm. 13C-NMR (126 MHz, DMSO-d6): δ=168.3 (1 C,
C
Tos), 132.7 (1 C, CHarom), 129.8 (2 C, 2×CHTos), 129.4 (2 C, 2×CHTos),
84.9 (1 C, C(CH3)3), 28.1 (3 C, C(CH3)3), 21.9 (1 C, Tos-CH3), 21.9 (1 C,
CH3), 14.8 (1 C, SCH3), 14.7 (1 C, SCH3) ppm. FT-IR: neat; v=2978 (w),
~
2927 (w), 1723 (m), 1601 (w), 1567 (m), 1546 (w), 1433 (w), 1387
(m), 1294 (m), 1255 (w), 1152 (w), 1125 (s), 1087 (w), 1040 (w), 1016
(w), 948 (w), 904 (w), 868 (w), 811 (w), 788 (w), 745 (m), 711 (w), 684
(w), 663 (m), 611 (w), 575 (w), 546 (m), 527 (w), 450 (w) cm-1. m.p.:
+
+
°
126 C (EtOAc). HRMS (ESI ): m/z calc. for C29H29N7O5S3Na1 [M+Na]
: 674.1285, found: 674.1279.
7-((tert-Butoxycarbonyl)(6-methyl-2-(methylthio)pyrido[3,2-d]
pyrimidin-7-yl)amino)-2-(methylthio)pyrido[3,2-d]
pyrimidin-6-yl 2-nitrobenzenesulfonate (30b)
C
aromSCH3), 164.2 (1 C, CaromSCH3), 160.1 (1 C, CHarom), 159.7 (1 C,
Compound 29 (13.5 mg, 27 μmol, 1.00 eq), 2-NosCl (6.8 mg,
27 μmol, 1.10 eq) and DMAP (0.3 mg, 3 μmol, 0.10 eq) were
t
Carom), 157.6 (1 C, Carom), 151.6 (1 C, NCO2 Bu), 146.3 (1 C, Carom), 146.0
(1 C, CHarom), 142.0 (1 C, Carom), 141.8 (1 C, Carom), 141.2 (1 C, NHCO),
135.6 (1 C, Carom), 134.1 (1 C, CHarom), 130.4 (1 C, CHarom), 128.1 (1 C,
°
suspended in THF (0.50 mL) cooled to 0 C and DIPEA (5.0 μL,
30 μmol, 1.10 eq) was added. The solution was stirred for 2.5 h
before it was poured into saturated aqueous NH4Cl-solution (5 mL)
and extracted with EtOAc (3×10 mL). The combined organic layers
were washed with brine (10 mL), dried over Na2SO4 and the solvent
was evaporated under reduced pressure. The crude product was
purified by column chromatography on silica (n-pentane/EtOAc 2:1
to 1:1) to give as single regioisomer compound 30b (14.0 mg,
21 μmol, 76%) as pale yellow foam. Rf =0.47 (n-pentane/EtOAc
Carom), 82.7 (1 C, C(CH3)3), 27.6 (3 C, C(CH3)3), 21.8 (1 C, CH3), 14.0 (1 C,
~
SCH3), 13.8 (1 C, SCH3) ppm. FT-IR: neat; v=2975 (w), 2925 (w), 2849
(w), 2544 (w), 2219 (w), 2188 (w), 2167 (w), 2102 (w), 2036 (w), 2003
(w), 1967 (w), 1709 (s), 1659 (s), 1606 (w), 1569 (m), 1548 (w), 1474
(w), 1446 (w), 1386 (s), 1310 (m), 1261 (w), 1241 (w), 1190 (w), 1144
(w), 1125 (s), 1043 (w), 1021 (w), 958 (w), 935 (w), 911 (w), 866 (w),
823 (w), 804 (w), 766 (w), 731 (w), 708 (w), 672 (w), 648 (w), 605 (m),
-1
°
579 (w), 561 (w), 542 (w), 474 (w), 447 (w) cm . m.p.: 305 C
1
1:1). H-NMR (500 MHz, CDCl3): δ=9.34 (s, 1H, CHarom), 8.91 (s, 1H,
decomposition (EtOAc). HRMS (ESI+): m/z calc. for C22H23N7O3S2Na1
[M+Na]+: 520.1196, found: 520.1205.
CHarom), 8.43 (d, J=7.52 Hz, 1H, CHNos), 8.05 (s, 1H, CHarom), 7.94 (s,
1H, CHarom), 7.89–7.83 (m, 3H, 3×CHNos), 2.82 (s, 3H, CH3), 2.62 (s, 3H,
SCH3), 2.61 (s, 3H, SCH3), 1.52 (s, 9H, C(CH3)3) ppm. 13C-NMR (126
Eur. J. Org. Chem. 2021, 1–20
17
© 2021 The Authors. European Journal of Organic Chemistry published
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