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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 18 9-Carboxymethyl Adenine Ethyl Ester (18) Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH'6. After stirring at 0 C. for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9H11N5O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6). The position of alkylation was verified by X-ray crystallography on crystals, which were obtained by recrystallization from 96% ethanol. Alternatively, 9-carboxymethyl adenine ethyl ester 18, can be prepared by the following procedure. |
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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 9 9-Carboxymethyl adenine ethyl ester (18) Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH~6. After stirring at 0 C. for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9 H11 N5 O2 found (calc.): C: 48.86 (48.65); H: 5.01 (4.91); N: 31.66 (31.42). 1 H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13 C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274 (10.4), 3246 (14.0), 3117 (5.3), 2989 (22.3), 2940 (33.9), 2876 (43.4), 2753 (49.0), 2346 (56.1), 2106 (57.1), 1899 (55.7), 1762 (14.2), 1742 (14.2), 1742 (1.0), 1671 (1.8), 1644 (10.9), 1606 (0.6), 1582 (7.1), 1522 (43.8), 1477 (7.2), 1445 (35.8) and 1422 (8.6). |
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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 47 9-Carboxymethyl adenine ethyl ester Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4N HCl was added to pH~6. After stirring at 0 C. for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9 H11 N5 O2 found (calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1 H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13 C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671 (1.8), 1644 (10.9), 1606 (0.6), 1582 (7.1), 1522 (43.8), 1477 (7.2), 1445 (35.8) and 1422 (8.6). |
3.4 g (20%) |
With potassium carbonate; In water; N,N-dimethyl-formamide; |
EXAMPLE 26 Synthesis of 9-carboxymethyladenine ethyl ester Adenine (10 g, 74 mmol) and potassium carbonate (10.29 g, 74 mmol) were suspended in DMF and ethyl bromoacetate (8.24 mL, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 mL). The combined filtrate was evaporated to dryness, in vacuo. Water (200 mL) was added to the yellowish-orange solid material and the pH adjusted to 6 with 4N HCl. After stirring at 0 C. for 10 minutes, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 mL). The title compound was isolated by filtration and washed thoroughly with ether. Yield: 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9 H11 N5 O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1 H-NMR (250 MHz; DMSO-d6): 7.25 (bs, 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13 C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1: 3855, 3274, 3246, 3117, 2989, 2940, 2876, 2753, 2346, 2106, 1899, 1762, 1742, 1742, 1671, 1644, 1606, 1582, 1522, 1477, 1445 and 1422. |
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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 18 9-Carboxymethyl adenine ethyl ester (18) Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH'6. After stirring at 0C for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220C. Anal. for C9H11N5O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6). |
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With potassium carbonate; In N,N-dimethyl-formamide; |
A. 9-Carboxymethyl adenine ethyl ester (31A) Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH'6. After stirring at 0C for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220C. Anal. for C9H11N5O2 fcund(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6). |
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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 40 9-Carboxymethyl adenine ethyl ester Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g, 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH'6. After stirring at 0 C. for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9H11N5O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6): (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6). |
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With potassium carbonate; In water; N,N-dimethyl-formamide; |
EXAMPLE 26 Synthesis of 9-carboxymethyladenine Ethyl Ester Adenine (10 g, 74 mmol) and potassium carbonate (10.29 g, 74 mmol) were suspended in DMF and ethyl bromoacetate (8.24 mL, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 mL). The combined filtrate was evaporated to dryness, in vacuo. Water (200 mL) was added to the yellowish-orange solid material and the pH adjusted to 6 with 4 N HCl. After stirring at 0 C. for 10 minutes, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 mL). The title compound was isolated by filtration and washed thoroughly with ether. Yield: 3.4 g (20%). M.p. 215.5-220 C. Anal. for C9H11N5O2 found(calc.): C: 48.86(48.65); H: 5.01(4.91); N: 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6): 7.25 (bs, 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8), and 1422(8.6). The position of alkylation was verified by X-ray crystallography on crystals, which were obtained by recrystallization from 96% ethanol. Alternatively, 9-carboxymethyladenine ethyl ester can be prepared by the following procedure. |
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With potassium carbonate; In N,N-dimethyl-formamide; |
EXAMPLE 30 9-Carboxymethyl Adenine Ethyl Ester Adenine (10.0 g, 74 mmol) and potassium carbonate (10.29 g; 74.0 mmol) were suspended in DMF and ethyl bromoacetate (8.24 ml, 74 mmol) was added. The suspension was stirred for 2.5 h under nitrogen at room temperature and then filtered. The solid residue was washed three times with DMF (10 ml). The combined filtrate was evaporated to dryness, in vacuo. The yellow-orange solid material was poured into water (200 ml) and 4 N HCl was added to pH'6. After stirring at 0 C. for 10 min, the solid was filtered off, washed with water, and recrystallized from 96% ethanol (150 ml). The title compound was isolated by filtration and washed thoroughly with ether. Yield 3.4 g (206). M.p. 215.5-220 C. Anal. for C9H11N5O2 found(calc.): C, 48.86(48.65); H, 5.01(4.91); N, 31.66(31.42). 1H-NMR (250 MHz; DMSO-d6) (s, 2H, H-2 & H-8), 7.25 (b. s., 2H, NH2), 5.06 (s, 2H, NCH2), 4.17 (q, 2H, J=7.11 Hz, OCH2) and 1.21 (t, 3H, J=7.13 Hz, NCH2). 13C-NMR. 152.70, 141.30, 61.41, 43.97 and 14.07. FAB-MS. 222 (MH+). IR: Frequency in cm-1 (intensity). 3855 (54.3), 3274(10.4), 3246(14.0), 3117(5.3), 2989(22.3), 2940(33.9), 2876(43.4), 2753(49.0), 2346(56.1), 2106(57.1), 1899(55.7), 1762(14.2), 1742(14.2), 1742(1.0), 1671(1.8), 1644(10.9), 1606(0.6), 1582(7.1), 1522(43.8), 1477(7.2), 1445(35.8) and 1422(8.6). |