Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Dimethylamine | HCID 674 | — |
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | HCID 58416746 | HCID 58416746 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Product | HCID 45254198 | HCID 45254198 | 37.1% |
Reaction Steps
To a solution of N-(4-((4-(3-(3-tert-Butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-chloroacetamide (Intermediate B) (50 mg, 0.08 mmol) in DCM (1.0 mL), DMF (0.1 mL) and DIPEA (17 μl, 0.1 mmol) was added dimethylamine (2.0M solution in THF) (41 μl, 0.08 mmol). The reaction mixture was heated to 40° C. and stirred for 12 hr. The crude reaction mixture was purified by column chromatography (12 g silica, 0-10% MeOH in DCM, gradient elution). Product fractions were concentrated in vacuo and the residue triturated with a mixture of diethyl ether, DCM and iso-hexane (2:1:2, 5.0 mL) to afford N-(4-((4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)methyl)pyridin-2-yl)-2-(dimethylamino) acetamide (Example 12) as an orange solid (18 mg, 35%): m/z 607 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 2.31 (6H, s), 2.39 (3H, s), 3.14 (2H, s), 5.39 (2H, s), 6.35 (1H, s), 7.01 (1H, d), 7.29 (1H, d), 7.35 (2H, d), 7.44 (2H, d), 7.65-7.55 (3H, m), 7.94 (1H, m), 8.38-8.28 (3H, m), 8.59 (1H, s), 8.79 (1H, s), 9.93 (1H, s).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US08293748B2 |
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| Source dataset | uspto-grants-2012_10 |
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| ORD ID | ord-301e90a4e68745ecba4981914ea8a99c |
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| Source note | uspto-grants-2012_10 |
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