HuagongsheHuagongshe Chemistry Print Report · For research reference only
Hydrochloric Acid → (S)-8-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-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 | Hydrochloric Acid | HCID 313 | — |
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 2733084 | — |
| Reactant | Methyl (s)-2-amino-3-(4'-cyano-[1,1'-biphenyl]-4-yl)propanoate | HCID 59337513 | — |
| Reactant | (S)-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 66719307 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Product | (S)-8-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester | HCID 67249301 | — |
Reaction Steps
(S)-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, HBTU and DIEA were dissolved in DMF (20 mL). (S)-2-Amino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester was added and the mixture stirred at r.t. for 16 h. The reaction mixture was poured into 1 N HCl and extracted with ethyl acetate. The organic extracts were combined and washed with 1 N HCl and 10% sodium carbonate, concentrated and purified by column chromatography on silica gel (hexanes-ethyl acetate) to afford the product (4.9 g). LCMS (m/z) 851.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US09175003B2 |
| Source dataset | uspto-grants-2015_11 |
| ORD ID | ord-2dadacb8150240dcb84d00b16cfc8a3f |
| Source note | uspto-grants-2015_11 |