HuagongsheHuagongshe Chemistry Print Report · For research reference only
4-Methylmorpholine → (3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | 4-Methylmorpholine | HCID 7972 | — |
| Reactant | 1-Hydroxybenzotriazole | HCID 75771 | — |
| Reactant | (3R,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester | HCID 58327389 | — |
| Reactant | L-Phenylalanine, 4-(2,3-dimethyl-4-pyridinyl)-, methyl ester, hydrochloride (1:2) | HCID 66719267 | — |
| Solvent | 1,2-Dichloroethane | HCID 11 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Product | (3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester | HCID 58327244 | — |
Reaction Steps
(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester (260 mg), (S)-2-amino-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester bis hydrochloride (190 mg), EDC (106 mg), and HOBt (78 mg) were suspended in 2 mL DCM and NMM (0.214 mL) added. The resulting mixture stirred at room temperature for 4 hours and loaded directly onto silica. The residue was purified by silica gel flash chromatography (hexanes to 1:1 hexanes/EtOAc to 1:1 hexanes/EtOAc+1% MeOH) to give 320 mg after drying under vacuum. LCMS: m/z 853.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US09175003B2 |
| Source dataset | uspto-grants-2015_11 |
| ORD ID | ord-2f72667a04524d65b06abbaa26ff9c91 |
| Source note | uspto-grants-2015_11 |