Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Methanol | HCID 887 | — |
| Reactant | Sodium Bicarbonate | HCID 516892 | — |
| Reactant | tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate | HCID 16217654 | — |
| Reactant | HCID 66823738 | HCID 66823738 | — |
| Catalyst | HCID 178418807 | HCID 178418807 | — |
| Solvent | Ethyl Acetate | HCID 8857 | — |
| Solvent | 1,4-Dioxane | HCID 31275 | — |
| Product | HCID 53469452 | HCID 53469452 | 91.4% |
Reaction Steps
A mixture of 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodofuro[3,2-c]pyridin-4-amine (142 mg, 0.267 mmol), 1-Boc-pyrazol-4-boronic acid pinacol ester (118 mg, 0.401 mmol), and PdCl2(dppf)-CH2Cl2 adduct (13 mg, 0.016 mmol) in 1,4-Dioxane (3 mL) and saturated aqueous sodium bicarbonate (0.80 mL, 0.800 mmol) was degassed with Nitrogen for 10 minutes in a microwave vial. The vial was then capped and the mixture was stirred at 120° C. in the microwave for 30 min. LCMS showed complete conversion to the de-Boc product. The mixture was cooled, poured into half-saturated aqueous NaHCO3 (25 mL), and extracted with ethyl acetate (2×25 mL). The extracts were washed with brine (1×25 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 24 g SiO2, 50%-100% EtOAc in hexanes gradient over 10 minutes, then EtOAc for 5 minutes, then 0-10% MeOH in EtOAc over 20 minutes) to give 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1H-pyrazol-4-yl)furo[3,2-c]pyridin-4-amine (121 mg, 0.244 mmol, 91% yield) as a white solid. LC/MS (ES) m/z=472 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.29 (t, J=8.34 Hz, 2H), 3.97 (s, 2H), 4.31 (t, J=8.46 Hz, 2H), 5.49 (s, 2H), 7.15-7.30 (m, 3H), 7.33 (d, J=8.08 Hz, 1H), 7.44 (s, 1H), 7.99-8.10 (m, 2H), 8.13 (d, J=8.08 Hz, 1H), 8.17-8.29 (m, 2H), 13.01 (br. s., 1H).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US08598156B2 |
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| Source dataset | uspto-grants-2013_12 |
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| ORD ID | ord-afa410a20f0647978d6ed1976844d264 |
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| Source note | uspto-grants-2013_12 |
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