HuagongsheHuagongshe Chemistry Print Report · For research reference only
Dicyclohexylamine → 4-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Dicyclohexylamine | HCID 7582 | — |
| Reactant | 4-Methylmorpholine | HCID 7972 | — |
| Reactant | Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 9886157 | — |
| Reactant | (2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acid | HCID 9899995 | — |
| Reactant | 3-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester | HCID 67606456 | — |
| Solvent | Diethyl Ether | HCID 3283 | — |
| Solvent | Ethyl Acetate | HCID 8857 | — |
| Solvent | N-methyl-2-pyrrolidone | HCID 13387 | — |
| Product | 4-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester | HCID 67607439 | — |
Reaction Steps
To a solution containing Cbz-Tle-OH.DCHA salt (4.1 g, 9.0 mmol) and HATU (3.8 g, 10 mmol) in NMP (50 mL) was added NMM (1.5 mL), followed by a solution of crude 22 (2.6 g, 7.5 mmol) in NMP (50 mL) at room temperature. The reaction mixture was stirred at room temperature. After 16 h, the reaction mixture was diluted with 10% EtOAc in Et2O, washed successively with water, 1N HCl, 1N NaOH, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue was purified by RP-HPLC (2″ Dynamax® C18; 10-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 3.5 g of 23 as white foam. Mass spectrum, m/z [688.3] (M+H)+.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US08415486B2 |
| Source dataset | uspto-grants-2013_04 |
| ORD ID | ord-33c5dd7a1f61474b9e8d7757c3a9f7a5 |
| Source note | uspto-grants-2013_04 |