H
ELVETICA
CHIMICA
ACTA – Vol. 88 (2005)
2615
AcONa·3 H2O (14 g, 110 mmol) and 2,6-diaminopyrimidin-4-one (6.66 g, 5.28 mmol) were solved in H2O
(110 ml), and the soln. was heated to 508. With a syringe pump, 2-chloro-2-oxopropanenitrile was added drop-
wise over 1 h. The suspension was stirred overnight. THF was subsequently evaporated in vacuo, and the sus-
pension was heated for 1 h to reflux. The suspension was filtered, and the residual material was washed with
acetone (3×50 ml) and H2O (3×50 ml). The bright yellow solid was dissolved in KOH soln. (6N, 50 ml).
After the addition of activated charcoal, the suspension was filtered, and the filtrate was brought to pH 6
with aq. HCl (30%). The precipitate was filtered and dried 24 h under vacuum at 508 to give 3 (7 g, 66 %).
White powder. M.p. >2508. IR (KBr): 3437m, 2229s, 1685s, 1510m, 1162w, 883w, 610w. 1H-NMR (600 MHz,
(D6)DMSO): 6.40 (s, NH2); 7.63 (s, CH); 10.72 (s, NH); 12.00 (s, NH). 13C-NMR (150 MHz, (D6)DMSO):
78.0; 84.4; 97.6; 114.8; 126.6; 150.5; 152.7; 156.4. HR-EI-MS (pos.): 175.0479 ([M+H]+, C7H5N5O+; calc.
175.0494).
3-Phthalimidopropanal (7). To a soln. of 3-phthalimidopropan-1-ol (0.5 g, 24 mmol) in CH2Cl2 (15 ml),
Dess–Martin periodinane (1.5 g, 36 mmol) was added. After stirring, the soln. was diluted with CH2Cl2 (30
ml), extracted with sat. aq. NaS2O3 (20 ml), NaHCO3 (20 ml), and brine (20 ml). The org. extract was evaporated
and dried. After removal of the solvents, the resulting residue was purified by FC (hexane/AcOEt 1:1) to give 7
(0.51 g, 95%). White solid. M.p. 121–1238. TLC (hexane/EtOAc 1 :2): Rf 0.45. IR (KBr): 3456m, 1768s, 1706s,
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1441s, 1403s, 1369s, 1324m, 1031s, 721s, 532m. H-NMR (200 MHz, CDCl3): 2.81 (t, CH2(2)); 3.98 (t, CH2(3));
7.63–7.66 (m, 3 arom. H); 7.75–7.79 (m, 2 arom. H); 9.75 (s, CH(1)). 13C-NMR (150 MHz, CDCl3): 31.8;
42.5; 123.5; 132.1; 134.1; 168.1; 199.5. EI-MS (pos.): 160 (100), 203 (8, M+). HR-EI-MS (pos.): 203.0573
([M+Na]+, C11H9NOþ3 ; calc. 203.0582).
2-[(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-1,3-dihydro-2H-isoindole-1,3-
dione (8). A soln. of 7 (5 g, 24.6 mmol) in MeCN (80 ml) was cooled to 08. DMSO (1.84 ml, 25.9 mmol) was
added dropwise, and Me3SiBr (3.35 ml, 35.9 mmol) was added slowly. The yellow colored soln. was stirred for
4 h at r.t.. A suspension of 2,6-diaminopyrimidin-4-one (3.1 g, 24.6 mmol) and AcOH·3 H2O (3.5 g,
25.1 mmol) in H2O (80 ml) was added slowly. The mixture was stirred overnight. A yellow precipitate was
formed. The bright yellow suspension was filtered and washed with acetone (3×80 ml) and H2O (3×80 ml).
The solid was dried to yield 8 (6.5 g, 85%). Bright yellow solid. M.p. >2508. IR (KBr): 3387s (br.), 2926m,
1770m, 1711s, 1627s, 1444m, 1361s, 1116w, 950w, 719m, 532m. 1H-NMR (200 MHz, (D6)DMSO): 4.82 (s,
CH2N); 6.06 (s, NH2); 6.36 (s, CH); 7.75–7.90 (m, 4 arom. H); 10.21 (s, NH); 10.80 (s, NH). 13C-NMR (150
MHz, (D6)DMSO): 27.9; 28.3; 35.0; 37.9; 98.4; 114.0; 123.2; 123.4; 132.1; 134.6; 151.7; 152.8; 163.7; 168.2.
HR-FAB-MS (pos.): 310.0943 ([M+H]+, C14H14N4O2þ ; calc. 310.0940).
tert-Butyl [(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)methy]carbamate (4). Method A.
Compound 3 (100 mg, 0.57 mmol) was suspended in DMF (5 ml), Pd/C (20 mg) was added, and the mixture was
stirred under H2 atmosphere (50 psi) for 24 h. The mixture was filtered and washed with DMF, and the solvents
were removed in vacuo. The red colored residue was dissolved in DMF (8 ml), and (Boc)2O (73 mg, 0.33 mmol)
and Et3N (46 ml, 0.33 mmol) were added. After stirring for 16 h, the soln. was washed with aq. NaHCO3 soln.
(10 ml), and the aq. phase was re-extracted with CH2Cl2 (4×10 ml). The combined org. fractions were washed
with brine (10 ml) and dried (MgSO4). The solvent was evaporated, and, after FC (MeOH/CHCl3 1 :10), 4 (10
mg, 10%) was obtained. White powder.
Method B. Compound 8 (800 mg, 2.64 mmol) was suspended in EtOH (30 ml), and NH2NH2 ·H2O (1.3 ml,
26.4 mmol) was added. The suspension was heated at reflux for 2 h at 808 and stirred for another 8 h at r.t. (the
reaction was monitored by TLC (BuOH/AcOH/H2O 2 :1 :1):Rf (4) 0.4). The solvent was evaporated, and preQ1
(crude) was obtained as a white solid, which was used without further purification.
preQ1 (crude; 200 mg, 1.12 mmol) was suspended in DMF (8 ml), Et3N (93 ml, 0.67 mmol) and (Boc)2O
(146 mg, 0.67 mmol) were added. After stirring for 8 h at r.t., more (Boc)2O (146 mg, 0.67 mmol) and Et3N
(93 ml, 0.67 mmol) were added. After 16 h, the soln. was washed with NaHCO3 (50 ml), and the aq. phase
was re-extracted with CH2Cl2 (4×50 ml). The combined org. fractions were extracted with brine (40 ml) and
dried (MgSO4). The solvent was evaporated, and, after FC (MeOH/CHCl3 1:10), 4 (50 mg, 31%) was obtained.
White powder. M.p. >2508. TLC (CHCl3/MeOH 5:1): Rf 0.40. IR (KBr): 3429s, 2978m, 2933m, 1673s, 1592s,
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1535m, 1249w, 1169w. H-NMR (600 MHz, (D6)DMSO): 1.33 (s, 3 Me); 4.13 (s, CH2); 6.08 (s, NH2); 6.46 (s,
CH); 7.04 (s, NH); 10.33 (s, NH); 10.79 (s, NH). 13C-NMR (150 MHz, (D6)DMSO): 27.7; 37.0; 78.1; 98.9;
113.7; 113.9; 116.3; 151.9; 152.7; 155.7; 160.1. EI-MS (pos.): 178 (100), 279 (6, [M+H]+). HR-EI-MS (pos.):
279.1359 ([M+H]+, C12H17N5Oþ3 ; calc. 279.1331).
7-(Aminomethyl)-7-deazaguanine (=preQ1 ; 5). Compound 4 (13 mg, 0.046 mmol) was dissolved at 08 in
TFA (1 ml). The soln. was stirred for 2 h at r.t. MeOH (5 ml) was added dropwise at 08, and the volatiles
were evaporated in vacuo. The trifluoroacetate salt of 5 (19 mg, quant.) was obtained. Bright yellow powder.