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102 Roque and Lowe
dissolved in acetone (30 ml) and water (60 ml) and NaHCO 3 (1.68 g, 20 mmol) in
water (30 ml) were added dropwise. The reaction mixture was stirred for2hat0°C.
The reaction was monitored by TLC (solvent system: ethyl acetate/methanol 95:5,
v/v) and stopped when no cyanuric chloride was detected. The resultant yellowish
solid product was filtered off, washed with hot water and heptane and dried in
vacuo over solid P 2 O 5 . Yield: 90% (5.15 g, 18.1 mmol). R f 0.6 (EtOAc/MeOH
95:5,v/v). 1 H-NMR(400MHz,[D 6 ]DMSO,25°C):7.34(s,1H,NH),7.65,7.67
(d,2H,ArH),7.87,7.89(d,2H,ArH),7.92(s,1H,NH),11.32(s,1H,NH). 13 C-
NMR (500 MHz, [D 6 ]DMSO, 25°C): 120.16, 128.42 (ArC), 129.63, 140.11
(ArC, quaternary), 166.88 (CONH 2 ), 166.18, 167.69, 169.41 (Ctriazine). MS
(EI, CONCEPT) calculated for C 10 H 7 Cl 2 N 5 O: 283.00, found 283.00. MS (ESI,
Q-tof) calculated for C 10 H 7 Cl 2 N 5 O (M+H) + : 284.0, found 284.0. Melting point
>250°C.
3.2.2.2. Synthesis of 4-[4-(4-Carbamoyl-Phenylamino)-6-Chloro-
[1,3,5]Triazin-2-Ylamino]-Butyric Acid
To a solution of 4-(4,6-dichloro-[1,3,5]triazin-2-ylamino)benzamide (1.98 g,
7 mmol) in DMF (100 ml) and water (15 ml), a mixture of 4-aminobutyric acid
(0.72 g, 7 mmol) in water (30 ml) and NaHCO 3 (0.58 g, 7 mmol) in water (30
ml) was added. The reaction was carried out at 45–50°C with constant stirring
for 24 h, monitored by TLC (solvent system: ethyl acetate/methanol 95:5,
v/v) and stopped when no 4-aminobutyric acid was detected by the ninhydrin
coloration test. The white precipitate formed was filtered off, washed with water
and dried in vacuo over solid P 2 O 5 . The white solid was dissolved in an aqueous
solution of K 2 CO 3 5% (w/v) and washed four times with ethylacetate. The
aqueous phase was neutralized with HCl (5 M) and the resultant white precipitate
filtered, washed with water and dried in vacuo over solid P 2 O 5 . Yield:
36% (0.87 g, 2.5 mmol). R f 0.4 (EtOAc/MeOH 95:5, v/v). 1 H-NMR (400 MHz,
[D 6 ]DMSO, 25°C): 1.71–1.82 (m, 2H, NHCH 2 CH 2 CH 2 COOH), 2.25–2.31
(m, 2H, NHCH 2 CH 2 CH 2 COOH), 3.26–3.29 (t, 2H, NHCH 2 CH 2 CH 2 COOH),
7.20 (s, 1H, NH), 7.76–7.84 (m, 4H, ArH and 1H, NH), 8.16, 8.24
(s, 2H, –CONH 2 ), 10.11, 10.23 (s, 1H, –COOH). 13 C-NMR (400 MHz,
[D 6 ]DMSO, 25°C): 24.31, 24.55, 31.38 (aliphatic CH 2 ), 119.47, 128.32
(ArC), 128.61, 128.67 (ArC quaternary), 142.04 (CONH 2 ), 165.80
(COOH), 168.30, 168.36, 174.65 (Ctriazine). MS (LSIMS, CONCEPT) calculated
for C 14 H 15 ClN 6 O 3 (M+H) + : 351.09, found 351.0. MS (ESI, CONCEPT)
calculated for C 14 H 15 ClN 6 O 3 (M+Na) + : 373.09, found 373.1. Melting point:
218–219°C.