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CAS No. : | 120747-85-5 | MDL No. : | MFCD09991890 |
Formula : | C5H7N3O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NUGGQZDIPXLGQW-UHFFFAOYSA-N |
M.W : | 125.13 | Pubchem ID : | 21615172 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Step 2: A slurry of 69 (31 g, 0.25 mol) in [CH2CI2] (500 ml) was cooled to [0 C] and slowly treated with SOC2 (55ml, 0.74 mol over 30 min). The reaction was then stirred overnight at [20 C.] The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid Preparation 7 was dried overnight in vacuo (38.4g, 52%, HCI salt). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 3h; | To a stirred solution of 2-aminopyrimidine-5-carbaldehyde (15, 500 mg, 4.06 mmol) in methanol (6 mL) was added sodium borohydride (200 mg, 5.28 mmol) in portions at 000. The resulting solution was slowly warmed to room temperature and was further stirred for 3 hours. After completion (monitored by TLC, 5% MeOH in DCM, Rf 0.3), thereaction mixture was quenched by addition of saturated aqueous NH4CI solution and the resulting reaction mixture was concentrated under vacuo. The residue was directly loaded over a short column of silica gel (100-200 mesh) and eluted with gradient elution of 100% DCM to 7.5% MeOH in DCM. Concentration of fractions containing desired product afforded (2-aminopyrimidin-5-yl)methanol (16) as a light yellow solid. Yield: 340mg (67%). 1H NMR (400 MHz, DMSO-d6) O 8.16 (5, 2H), 6.50 (brs, 2H), 4.99 (t, 1H),4.26 (d, 2H). GCMS [mlz]: 125.0 |
62% | With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 4.33h; | A solution of aldehyde (50 g, 0.41 mol) [see, for example, WO 0232893] in MeOH (300 mL) was cooled to 0 C. and carefully treated with NaBH4 (20 g, 0.53 mol in 6 batches) over 20 minutes. The reaction was then allowed to warm to 20 C. and was stirred for 4 hours. The mixture was again cooled to 0 C., carefully quenched with saturated aqueous NH4Cl, and concentrated. Flash chromatography (5-10% 7N NH3-MeOH/CH2Cl2) provided the primary alcohol (31 g, 62%) as a light yellow solid. |
62% | With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 260h; | A solution of aldehyde (50 g, 0.41 mol) [WO 0232893] in MeOH (300 mL) was cooled to 0 C and carefully treated with NaBH4 (20g, 0.53 mol in 6 batches) over 20 minutes. The reaction was then allowed to warm to 20 C and was stirred for 4 hours. The mixture was again cooled to 0 C, carefully quenched with saturated aqueous NH4CI, and concentrated. Flash chromatography (5- 10% 7N NH3-MeOH/CH2CI2) provided the primary alcohol (31g, 62%) as a light yellow solid |
62% | Step 1: A solution of 68 (50 g, 0.41 mol) in CH30H (300 ml) was cooled to [0 C] and carefully treated with NaBH4 (20g, 0.53 mol in 6 batches) over 20 min. The reaction was then allowed to warm to 20 [C] and was stirred for 4 h. The mixture was again cooled to 0 [C,] carefully quenched with saturated aqueous [NH4CI,] and concentrated. Flash chromatography (5-10% 7N [NH3-CH3OH/CH2CI2)] provided 69 (31g, 62%) as a light yellow solid. | |
With sodium tetrahydroborate; In methanol; water; N,N-dimethyl-formamide; | Example 85 (2-Amino-pyrimidin-5-yl)-methanol A solution of 2-Amino-pyrimidine-5-carbaldehyde (500 mg) in DMF:water:MeOH (4:1:1, 30 mL) was treated with NaBH4 (200 mg, excess) and stirred at RT for 30 minutes. The product could not be extracted into organics so the solvents were removed and the crude product was used directly in the subsequent reaction. MS 126 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With thionyl chloride; In dichloromethane; at 0 - 20℃; | A slurry of alcohol (31 g, 0.25 mol) from Preparative Example 400, Step A in CH2Cl2 (500 mL) was cooled to 0 C. and slowly treated with SOCl2 (55 mL, 0.74 mol over 30 minutes). The reaction was then stirred overnight at 20 C. The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid was dried overnight in vacuo (38.4 g, 52%, HCl salt). |
52% | With thionyl chloride; In dichloromethane; at 0 - 20℃; | A slurry of alcohol (31 g, 0.25 mol) from Preparative Example 216, Step A in CH2CI2 (500 mL) was cooled to 0 C and slowly treated with SOCI2 (55mL, 0.74 mol over 30 minutes). The reaction was then stirred overnight at 20 C. The material was concentrated, slurried in acetone, and then filtered. The resulting beige solid was dried overnight in vacuo (38.4g, 52%, HCI salt). |
With thionyl chloride; In dichloromethane; at 0 - 20℃; for 16h; | To a stirred suspension of 130 (500 mg, 4 mmol) in DCM (10 mL) was added SOd2 (1 mL) drop wise atO C. After completion of the addition, the reaction mixture was allowed to RTforl6 h. The reaction mixture was concentrated under reduced pressure to get 290 mg of crude 131 as HCI salt. The crude compound was as such taken for next step without any further purification. To a stirred solution of 6-003 (582 mg, 2 mmol) in DMF (10 mL) was added 131 (290 mg, crude, 2 mmol) and K2C03 (828 mg,6 mmol) at RT. The reaction mixture was irradiated under microwave at 80 C for 1 h. The progress of the reaction was monitored by TLC. The solvent was removed under reduced pressure to get the crude material. The crude compound was purified by Grace Purification system [C-18 column with 0.01 % HCOOH in water and acetonitrile] to afford 500 mg of crude 6-225. The crude compound was purified by prep. HPLC purification to get 6-225 (60 mg, 4 % two steps) as a white solid. 1H NMR (400 MHz,DMSO-d6): O 9.03 (brs, 1 H), 8.53 (brd, J = 7.8 Hz, 1H), 8.31 (s, 2H), 7.35- 7.30 (d, J = 7.3 Hz, 1H),7.23 (d, J= 7.3 Hz, 1H), 7.09-6.84 (m, 2H), 5.13-4.85 (m, 4H), 4.37-4.22 (m, 1H), 2.43 (s, 3H), 2.11(qd, J = 13.3, 6.3 Hz, 1 H), 0.92 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3HLC-MS: m/z 399.22 [M+H].HPLC purity: 94.03% (220 nm) and chiral HPLC purity is 98.99% (229 nm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In hydrogenchloride; | (2-Chloro-pyrimidin-5-yl)-methanol A solution of <strong>[120747-85-5](2-Amino-pyrimidin-5-yl)-methanol</strong> (400 mL, 3.2 mmol) was dissolved in HCl (aq. 3M, 20 mL) and treated with NaNO2 (aq. 1N, 20 mL). The reaction was stirred at 0° C. for 18 hours. The mixture was basified with K2CO3 (aq.) then extracted with DCM (3*50 mL). The organics were washed with more K2CO3 (aq.) and the organics concentrated to give the pure product as needles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With thionyl chloride; In dichloromethane; at 20℃; for 16h; | To a stirred solution of <strong>[120747-85-5](2-aminopyrimidin-5-yl)methanol</strong> (16, 340 mg, 2.72 mmol) in DCM (5 mL) was added thionyl chloride (0.6 mL, 8.16 mmol) at 0C. The resulting solution was slowly warmed to room temperature and was stirred for 16 hours. After complete consumption of compound 16 (monitored by TLC, 5% MeOH in DCM, Rf 0.3), the reaction mixture was concentrated under vacuo. The residue was triturated with acetone to afford the hydrochloride salt of 5-(chloromethyl)pyrimidin-2-amine (17) as an off-white solid. Yield: 340 mg (70%).1H NMR (400 MHz, DMSO-d6) O 8.57 (5, 2H), 7.90 (brs, 3H), 4.71 (5, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With methanol; sodium tetrahydroborate; at 0 - 20℃; for 2h; | General procedure: To a solution of aldehyde in the indicated solvent is added sodium borohydride at 0 C. After stirring at room temperature for 2 hours, water is added and the mixture is concentrated.Following Procedure C using crude 4 (1.0 g, 6.35 mmol), MeOH, and sodium borohy dride (360 mg, 9.55 mmol), then quench with water (1 mL) and purify with silica gel column chromatography (MeOH:DCM := 1 :50) to give AS as a solid (650 mg, 65% yield). (MS: [M+H]+ 160.1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | With dmap; triethylamine; In tetrahydrofuran; at 20℃; | To a solution of A13 (2.0 g, 15.9 rnrnoi), TEA (6.47 g, 63.9 rnmoi), and DMAP (1.95 rnrnol) in THF (30 rnL) is added di-tert-butyl dicarbonate (12.2 g, 55.9 rnmol). After stirring at room temperature overnight, the mixture is concentrated and dissolved in EA (100 mL), washed th HC1 solution (0.5 M, 30 rnL) and brine (30 rnL). dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (EA:PE 1:5) to give 74 as a white solid (680 mg, 10% yield). (MS:[M+H] 4262) |
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