CHEMISTRY & BIODIVERSITY – Vol. 12 (2015)
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5-Methyl-2-phenyl-N-[4-(trifluoromethyl)phenyl][1,3]oxazolo[5,4-d]pyrimidin-7-amine (9d). Yield:
65%. M.p. 156–1588 (CH2Cl2/PE). IR (KBr): 3411, 3318, 1610, 1324, 1067, 1015, 837. 1H-NMR (CDCl3):
8.13 (d, J¼7.8, 2 arom. H); 7.93 (d, J¼8.7, 2 arom. H); 7.60 (d, J¼8.7, 2 arom. H); 7.48 (m, 3 arom. H);
2.70 (s, Me). EI-MS: 370 (Mþ ). Anal. calc. for C19H13F3N4O (370.1041): C 61.62, H 3.54, N 15.13; found:
C 61.51, H 3.45, N 15.02.
N-(3-Chloro-4-fluorophenyl)-5-methyl-2-phenyl[1,3]oxazolo[5,4-d]pyrimidin-7-amine (9e). Yield:
56%. M.p. 160–1618 (CH2Cl2/PE). IR (KBr): 3387, 3087, 1626, 1483, 1412, 1092, 744. 1H-NMR
((D6)DMSO): 10.40 (s, NH); 8.24 (dd, J¼6.9, 2.7, 1 arom. H); 8.16 (m, 2 arom. H); 7.92 (m, 1 arom. H);
7.64 (m, 3 arom. H); 7.42 (t, J¼9.0, 1 arom. H); 2.58 (s, Me). EI-MS: 354 (Mþ ). Anal. calc. for
C18H12ClFN4O (354.0684): C 60.94, H 3.41, N 15.79; found: C 60.65, H 3.80, N 15.43.
N-(2,4-Difluorophenyl)-5-methyl-2-phenyl[1,3]oxazolo[5,4-d]pyrimidin-7-amine (9f). Yield: 33%.
M.p. 150–1528 (CH2Cl2/PE). IR (KBr): 3403, 3064, 1626, 1456, 1408, 751. 1H-NMR ((D6)DMSO): 8.14
(d, J¼8.4, 1 arom. H); 7.90 (m, 2 arom. H); 7.71 (d, J¼8.4, 2.1, 1 arom. H); 7.37 (m, 3 arom. H); 7.11 (t, J¼
7.8, 1 arom. H); 2.57 (s, Me). EI-MS: 338 (Mþ ). Anal. calc. for C18H12F2N4O (338.0979): C 63.90, H 3.58,
N 16.56; found: C 63.73, H 3.60, N 16.68.
2,5-Dimethyl-N-phenyl[1,3]oxazolo[5,4-d]pyrimidin-7-amine (9g). Yield: 8%. M.p. 102–1038
(CH2Cl2/PE). IR (KBr): 3406, 3067, 1634, 1518, 1464, 809, 569. 1H-NMR ((D6)DMSO): 8.23 (s, 2 arom.
H); 7.68 (s, 3 arom. H); 4.47 (s, ArÀMe); 2.74 (s, Me). EI-MS: 240 (Mþ ). Anal. calc. for C13H12N4O
(240.1011): C 64.99, H 5.03, N 23.32; found: C 64.81, H 4.87, N 23.55.
N-(3-Chloro-4-fluorophenyl)-2-(4-methoxyphenyl)-5-methyl[1,3]oxazolo[5,4-d]pyrimidin-7-amine
(10). Yield: 3%. M.p. 199–2008 (CH2Cl2/PE). IR (KBr): 3413, 3324, 2841, 1638, 1501, 1258, 829.
1H-NMR (CDCl3): 8.13 (d, J¼8.7, 2 arom. H); 8.06 (dd, J¼8.7, 2.4, 1 arom. H); 7.62 (m, 1 arom. H, NH);
7.16 (t, J¼8.7, 1 arom. H); 7.04 (d, J¼8.7, 2 arom. H); 3.90 (s, MeO); 2.71 (s, Me). EI-MS: 384 (Mþ ).
Anal. calc. for C19H14ClFN4O2 (384.0789): C 59.31, H 3.67, N 14.56; found: C 58.98, H 3.73, N 14.71.
4-{7-[(3-Chloro-4-fluorophenyl)amino]-5-methyl[1,3]oxazolo[5,4-d]pyrimidin-2-yl}phenol (9h).
BBr3 (0.35 ml, 3.7 mmol) was added to a soln. of 10 (300 mg, 0.78 mmol) in anh. CH2Cl2 (20 ml) at 08.
The mixture was stirred at r.t. for 24 h. The soln. was cooled to 08, stirred for another 20 min after adding
20 ml of ice water, and then extracted with CH2Cl2 (2Â30 ml) and AcOEt (2Â30 ml). The org. layer was
separated, dried (Na2SO4), and filtered. The solvent was evaporated until dryness. The residue was
purified by CC (SiO2; AcOEt/PE 1:5) to give 9h (202 mg, 70%). Yellow solid. M.p. 236–2388 (CH2Cl2/
1
PE). IR (KBr): 3415, 3314, 2840, 1655, 1500, 1416, 1265, 768. H-NMR ((D6)DMSO): 10.39 (s, OH);
10.30 (s, NH); 8.24 (dd, J¼6.9, 2.4, 1 arom. H); 8.00 (d, J¼8.7, 2 arom. H); 7.92 (m, 1 arom. H); 7.41 (t, J¼
9.0, 1 arom. H); 6.99 (d, J¼8.7, 2 arom. H); 2.57 (s, Me). EI-MS: 370 (Mþ ). Anal. calc. for
C18H12ClFN4O2 (370.0633): C 58.31, H 3.26, N 15.11; found: C 57.92, H 3.35, N 15.36.
N-(3-Chloro-4-fluorophenyl)-5-methyl-2-{4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}[1,3]oxa-
zolo[5,4-d]pyrimidin-7-amine (9i). KI (2 mg, 0.01 mmol) was added to a soln. of 9h (28 mg, 0.076 mmol),
1-(3-chloropropyl)-4-methylpiperazine hydrochloride (32 mg, 0.15 mmol), and K2CO3 (42 mg,
0.30 mmol) in acetone (5 ml). The mixture was stirred at 568 for 24 h. The precipitate was collected
on a funnel and rinsed with CH2Cl2 (10 ml) followed by MeOH (20 ml). The solvent was evaporated until
dryness. The residue was purified by CC (SiO2; AcOEt) to furnish 9i (18 mg, 47%). White solid. M.p.
148–1508 (CH2Cl2/PE). IR (KBr): 3446, 2922, 2850, 1628, 1498, 1249, 841. 1H-NMR (CDCl3): 8.12 (d, J¼
9.0, 2 arom. H); 8.05 (m, 1 arom. H); 7.60 (m, 1 arom. H); 7.38 (s, NH); 7.16 (t, J¼8.7, 1 arom. H); 7.03 (d,
J¼9.0, 2 arom. H); 4.11 (t, J¼6.3, CH2O); 2.72 (s, Me); 2.54 (m, 5 CH2N); 2.30 (s, MeN); 2.02 (t, J¼
6.9 Hz, CH2). EI-MS: 510 (Mþ ). Anal. calc. for C26H28ClFN6O2 (510.1946): C 61.11, H 5.52, N 16.45;
found: C 61.36, H 5.40, N 16.50.
N-(3-Chloro-4-fluorophenyl)-5-methyl-2-{4-[2-(morpholin-4-yl)ethoxy]phenyl}[1,3]oxazolo[5,4-
d]pyrimidin-7-amine (9j). When the same procedure as for preparing 9i was used, from 9h (30 mg,
0.08 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (30 mg, 0.16 mmol), 9j was obtained (26 mg,
1
67%). M.p. 174–1768 (CH2Cl2/PE). IR (KBr): 3450, 2918, 2849, 1628, 1499, 1256, 1111, 832. H-NMR
(CDCl3): 8.04 (d, J¼8.7, 2 arom. H); 7.98 (d, J¼3.9, 1 arom. H); 7.53 (m, 1 arom. H); 7.41 (s, NH); 7.09 (t,
J¼8.7, 1 arom. H); 6.92 (d, J¼8.7, 2 arom. H); 4.31 (s, CH2O); 3.72 (s, 2 CH2O); 2.84 (s, CH2N); 2.64 (s,
Me); 2.60 (s, 2 CH2N). EI-MS: 483 (Mþ ). Anal. calc. for C26H28ClFN6O2 (483.1473): C 61.11, H 5.52,
N 16.45; found: C 61.36, H 5.40, N 16.50.