HuagongsheHuagongshe Chemistry Print Report · For research reference only
Trifluoroacetic acid → (1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Trifluoroacetic acid | HCID 6422 | — |
| Reactant | Triethylsilane | HCID 12052 | — |
| 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 | {(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester | HCID 57892933 | — |
| Reactant | (1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl ester | HCID 59165438 | — |
| Reactant | (1R,2R,4R)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid tert-butyl ester | HCID 59204175 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Product | (1R,2S)-1-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methylcarbamoyl-methyl)-carbamoyl]-2,2-dimethyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester | HCID 59204178 | 74% |
Reaction Steps
To a solution of compound 35 (30 mg, 0.050 mmol) in methylene chloride (1.5 mL) were added triethylsilane (21 □L, 0.132 mmol) and TFA (1.5 mL). The mixture was stirred for 2 h at room temperature and was then evaporated and coevaporated with toluene. The amine 38 (1.3 eq) was deprotected in the same manner as compound 35 and was then coupled to deprotected compound 35 using the same HATU coupling conditions as in the synthesis of 34. The crude product was extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification using HPLC (MeOH/water 9:1+0.2% triethylamine) provided compound 39 (30 mg, 74%) as a colorless solid.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US07671032B2 |
| Source dataset | uspto-grants-2010_03 |
| ORD ID | ord-3d7bd8536cd844a1893f40922ebdb776 |
| Source note | uspto-grants-2010_03 |