PAPER
Unusual Ring Closure Reaction of Amides with Pyrimidines
2129
HRMS: m/z found (M + 1)+, 481.9836 (FAB). C18H17 Br N3O4S2 re-
HRMS: m/z found (M – 1)+, 513.1621. C25H26FN4O5S requires (M
quires (M + 1), 481.9844 (M + 1).
– 1), 513.1608.
1H NMR: δ = 3.3 (s, 6 H), 7.50 (d, J = 8 Hz, 4 H), 7.95 (d, J = 8 Hz,
4Ca
4 H), 9.20 (s, 2 H).
Yield: 87%; mp 215–217 ºC.
13C NMR: d = 21.4, 121.0, 128.9, 129.9, 136.2, 145.9, 154.1, 161.0.
HRMS: m/z found M+:383.9874. C13H13BrN4O3S requires M
383.9892),
Alkylation of Sulfonamidoyrimidines 2 A–C with Bromoaceta-
mides 3 a–f; General Procedure
8Ca
Yield: 8%.
Diisopropylethylamine (0.65 mL, 3.6 mmol) was slowly added to
the corresponding sulfonamidopyrimidines 2 (3 mmol) in DMF (12
mL) under argon over 40 min. The corresponding bromoacetamide
3 (3.6 mmol) was added to the mixture and stirred for 16 h at r.t. The
crude mixture was poured into H2O (200 mL) affording the alkylat-
ed derivatives 4 or the Michael addition products 6 besides small
amounts of 8.
HRMS: m/z found M+, 383.9879. C13H13BrN4O3S requires M,
383.9892.
Isolation of Compounds 4Ba and 6Cb–d
When the reaction product did not precipitate, the aqueous phase
was extracted with EtOAc (3 × 50 mL), the combined extracts were
dried (Na2SO4) and the solvent evaporated. The residue was chro-
matographed on silica using CH2Cl2/THF (9:1) or CH2Cl2/EtOAc
(7:3) to afford compounds 4Ba and 6Cb–d. Compounds 6Cb–d,
were obtained as gums which could not be induced to crystallise.
4Aa
Yield: 85%; mp 213–215 ºC.
HRMS: m/z found (M + 1)+, 307.0865 (FAB). C13H15N4O3S re-
quires (M + 1), 307.0865.
4Ba
Yield: 65%; mp 191–193 ºC.
8Aa
Yield: 7%; mp 220–222 ºC.
HRMS: m/z found M+, 420.1449. C19H24N4O5S requires M,
420.1467.
HRMS: m/z found (M + 1)+, 307.0858 (FAB). C13H15N4O3S re-
quires (M + 1), 307.0865.
6Cb
Yield: 71%.
4Ab
HRMS: m/z found M+, 492.0101. C19H17BrN4O5S requires M,
Yield: 89%; mp 196–198 ºC.
492.0103.
HRMS: m/z found M+, 382.1097. C19H18N4O3S requires M,
382.1100.
6Cc
Yield: 75%.
4Ac
HRMS: m/z found M+, 569.9203. C19H16Br2N4O5S requires M,
Yield: 70%; mp 187–189 ºC.
569.9208.
HRMS: m/z found M+, 460.0201. C19H17BrN4O3S requires M,
460.0205.
6Cd
Yield: 80%.
4Ad
HRMS: m/z found M+, 529.9709. C19H16BrClN4O5S requires M,
Yield: 91%; mp 254–257 ºC.
529.9713.
HRMS: m/z found (M + 1)+, 417.0783 (FAB). C19H18ClN4O3S re-
quires (M + 1), 417.0788.
Conversion of 4Ac to 6Ac
4Ae
When the alkylated product 4Ac was stored in THF solution at room
temperature for a week in the presence of catalytic amounts of di-
isopropylethylamine, the corresponding product 6Ac was obtained;
yield: 20%; mp 196–198 ºC.
Yield: 67%; mp 214–216°C.
HRMS: m/z found M+, 400.1008. C19H17FN4O3S requires M,
400.1005.
4Af
HRMS: m/z found M+, 460.0201. C19H17BrN4O3S requires M,
Yield: 80%; mp 226–228 ºC.
460.0205.
HRMS: m/z found M+, 418.0909. C19H16F2N4O3S requires M,
418.0911.
Imidazo[1,2-a]pyrimidines 5; General Procedure
The alkylated derivatives 4Aa, 4Ab, 4Ac, 4Af, 4Ba, 4Ca and the
hexahydroimidazo[1,2-c]pyrimidines 6Bb, 6Bd (2 mmol) were
heated at reflux with trifluoroacetic acid (15 mL, 50 mmol) in
CH2Cl2 (35 mL) under argon for 4 h.. The solvent was evaporated
and the residue extracted with EtOAc. The organic phase washed
with aq NaHCO3 solution, dried (Na2SO4) and concentrated. The
residue was purified by column chromatography using CH2Cl2/
EtOAc (3:1) affording imidazo[1,2-a]pyrimidines 5.
6Bb
Yield: 69%; mp 228–230 ºC.
HRMS: m/z found M+, 495.1706. C25H27N4O5S requires M,
495.1702.
6Bc
Yield: 74%; mp 248–250 ºC.
HRMS: m/z found M+, 574.0864. C25H27BrN4O5S requires M,
574.0886.
5Aa
Yield: 40%; mp 255–257 ºC.
HRMS: m/z found M+, 230.0413; C8H5F3N4O requires M,
230.0415.
6Bd
Yield: 75%; mp 249–251 ºC.
HRMS: m/z found (M – 1)+, 529.1310. C25H26ClN4O5S requires (M
– 1), 529.1312.
5Ab
Yield: 75%; mp 235–237 ºC.
HRMS: m/z found M+, 306.0734. C14H9F3N4O requires M,
306.0728.
6Be
Yield: 80%; mp 250–252 ºC.
Synthesis 1999, No. 12, 2124–2130 ISSN 0039-7881 © Thieme Stuttgart · New York