Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| 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 | (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride | HCID 67212109 | — |
| Reactant | N-[(1S)-1-(5-chloro-2-piperidin-4ylphenyl)ethyl]acetamide hydrochloride | HCID 68520212 | — |
| Solvent | Water | HCID 962 | — |
| Product | MK-0493 free base | HCID 11642422 | 99.1% |
Reaction Steps
N,N-diisopropylethylamine (5.86 mL, 33.6 mmol) was added to a stirred suspension of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride (3-9) (3.07 g, 9.61 mmol), N-[(1S)-1-(5-chloro-2-piperidin-4-ylphenyl)ethyl]acetamide hydrochloride (3.05 g, 9.61 mmol), and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluoro-phosphate (4.38 g, 11.5 mmol) in N,N-dimethylfoimamide (20 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient elution; 0-9% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) provided 3-10 (5.2 g) as a foam m/z (ES) 546 (MH+).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US06818658B2 |
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| Source dataset | uspto-grants-2004_11 |
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| ORD ID | ord-49eeaa2b4a614b9db44f2795ed66b821 |
|---|
| Source note | uspto-grants-2004_11 |
|---|
