Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Acetic Acid | HCID 176 | — |
| Reactant | 1-Methylpiperazine | HCID 53167 | — |
| Reactant | Sodium Bicarbonate | HCID 516892 | — |
| Reactant | Sodium triacetoxyborohydride | HCID 5049666 | — |
| Reactant | HCID 22347189 | HCID 22347189 | — |
| Solvent | Water | HCID 962 | — |
| Solvent | 1,1-Dichloroethane | HCID 6365 | — |
| Product | HCID 22347037 | HCID 22347037 | 21% |
Reaction Steps
Sodium triacetoxyborohydride (67 mg, 0.319 mmol) was added to a mixture of 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]benzaldehyde (100 mg, 0.245 mmol), 4-methylpiperazine (37 mg, 0.369 mmol), glacial acetic acid (35 mg, 0.589 mmol) in dichloroethane (4 mL). After stirring at room temperature over night, more sodium triacetoxyborohydride (67 mg, 0.319 mmol) was added and the reaction mixture was stirred over night. Water (2 mL) was added and followed by sodium bicarbonate (250 mg). After stirring vigorously for 1 hour, the layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichlromethane/methanol (97:3 to 80:20) as mobile phase to give 1-{4-[(4-methylpiperazino)methyl]phenyl}-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (25 mg, 21%). 1H NMR (DMSO-d6) δ 2.30 (s, 3H), 2.48(bm, 8H), 3.56 (s, 3H), 5.75 (bs, 2H), 7.11 (d, J=8.50, 2H), 7.18 (m, 3H), 7.40 (m, 2H), 7.48 (d, J=8.50 Hz, 2H), 7.29 (d, J=8.63 Hz, 2H), 8.12 (d, J=8.50 Hz, 2H), 8.47 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=492.2, Rt=2.97 min.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US06921763B2 |
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| Source dataset | uspto-grants-2005_07 |
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| ORD ID | ord-3d00e8176e1d4472abc853b61a07f8f5 |
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| Source note | uspto-grants-2005_07 |
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