Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Hydrochloric Acid | HCID 313 | — |
| Reactant | Carbonate Ion | HCID 19660 | — |
| Reactant | HCID 67263949 | HCID 67263949 | — |
| Reactant | N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide | HCID 86633854 | — |
| Solvent | Methanol | HCID 887 | — |
| Solvent | 2-Methoxyethanol | HCID 8019 | — |
| Solvent | 1,4-Dioxane | HCID 31275 | — |
| Product | HCID 67264489 | HCID 67264489 | — |
Reaction Steps
Into a microwave vial, 8-amino-1-ethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (75 mg, 0.00036 mol), N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (113 mg, 0.332 mmol), 4 M of hydrogen chloride in dioxane (0.2 mL), and 2-methoxyethanol (2.3 mL) were added. The reaction was then heated in microwave at 120 degree Celsius for one hour. MP-carbonate (3.16 mmol/g loading; 263 mg, 0.83 mmole) and methanol (10 mL) were added. The mixture was stirred at room temperature over night. The solid was filtered and washed with methanol. The desired product was isolated via column chromatography with DCM and methanol as eluant. The collected fractions afforded N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a yellow solid (35 mg, 19%). 1H-NMR (DMSO-D6, 400 MHz): δ 9.19 (s, 1H), 7.94 (s, 1H), 7.51 (d, 1H), 7.12 (d, 1H), 7.07 (d, 1H), 6.97 (s, 1H), 6.75 (d, 1H), 5.99 (bs, 1H), 3.70-3.88 (m, 1H), 3.25-3.52 (m, 7H), 2.92 (s, 3H), 1.97-2.10 (m, 2H), 1.69 (bs, 2H), 1.15-1.48 (m, 4H), 1.08 (t, 3H) LCMS (ESI+) 508.26 (M+H). MP 216-220° C.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US08552186B2 |
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| Source dataset | uspto-grants-2013_10 |
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| ORD ID | ord-45935b82ebee4072ad5ada02b0697f1a |
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| Source note | uspto-grants-2013_10 |
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