Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Acetone | HCID 180 | — |
| Reactant | Sodium Carbonate | HCID 10340 | — |
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | Sodium triacetoxyborohydride | HCID 5049666 | — |
| Reactant | HCID 67045227 | HCID 67045227 | — |
| Solvent | dichloromethane N,N-dimethylformamide | HCID 22350042 | — |
| Product | HCID 67045360 | HCID 67045360 | 62.3% |
Reaction Steps
DIEA (0.023 mL, 0.133 mmol) was added to a solution of (S)—N-(4-(3-(aminomethyl)pyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (70 mg, 0.13 mmol; Example 3A) and propan-2-one (77.4 mg, 1.33 mmol) in CH2Cl2:DMF (1:1, 3 mL), followed by the addition of NaBH(OAc)3 (57 mg, 0.26 mmol). The reaction was stirred for 30 minutes. The reaction mixture was then poured into a solution of Na2CO3 and extracted into CH2Cl2. The organic phases were combined, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC (Gilson system). The isolated product was then dissolved in minimal CH2Cl2 (with MeOH to aid solubility) and added to 1M HCl in ether (10 mL). The solid formed was collected to provide (S)—N-(5-bromo-4-(3-((isopropylamino)methyl)pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (40 mg, 53% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.08 (d, 1H), 10.58 (s, 1H), 9.32 (d, 1H), 8.98 (dd, 1H), 8.76 (dt, 1H), 8.32 (s, 1H), 7.99 (dd, 1H), 7.67 (d, 1H), 3.77-3.73 (m, 1H), 3.60-3.52 (m, 2H), 3.39-3.34 (m, 1H), 3.23-3.16 (m, 1H), 2.91-2.85 (m, 2H), 2.73-2.66 (m, 1H), 2.14-2.07 (m, 1H), 1.74-1.64 (m, 1H), 1.22 (d, 6H); LCMS (APCI+) m/z 459.1, 460.1 (M+H)+.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US09365568B2 |
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| Source dataset | uspto-grants-2016_06 |
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| ORD ID | ord-b4bdbf34b97548b7b37da722b91e83d0 |
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| Source note | uspto-grants-2016_06 |
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