Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Benzenesulfonic Acid | HCID 7371 | — |
| Reactant | (7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine | HCID 86704483 | — |
| Reactant | 1-(5-amino-2-(2-(tert-butyldimethylsilyl)oxyethoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one | HCID 86704486 | — |
| Solvent | Isopropanol | HCID 3776 | — |
| Product | Benzenesulfonic Acid | HCID 7371 | — |
| Product | 4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxyethoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrile | HCID 71811557 | — |
Reaction Steps
A mixture of 1-(5-amino-2-(2-(tert-butyldimethylsilyl)oxyethoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (200 mg), (7R,8aS)—N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (120 mg), and benzenesulfonic acid (120 mg) in IPA (2 mL) was heated to 80° C. overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-20%) to give desired product with benzenesulfonic acid. The methanol solution of the salt was passed through an ion-exchange resin column to remove acid to give the free base of compound 78 (120 mg, 57%).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09169249B2 |
|---|
| Source dataset | uspto-grants-2015_10 |
|---|
| ORD ID | ord-50f98e2a38074d1da4b11d78c8cc9a28 |
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| Source note | uspto-grants-2015_10 |
|---|
