Acetone → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic Acid 2-methoxyethyl Ester
Reaction equation
CC.[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([F:39])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]([CH2:33][C@@H:34]([OH:38])[C:35]([OH:37])=[O:36])[NH:18][C:19]([C:21]3[O:25][N:24]=[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[CH:22]=3)=[O:20])=[CH:12][CH:11]=2)[CH:9]=1.CCN([CH2:45][CH3:46])CC.C[C:48](C)=[O:49]>>[CH3:48][O:49][CH2:45][CH2:46][O:36][C:35](=[O:37])[C@H:34]([OH:38])[CH2:33][N:17]([CH2:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]2[CH:9]=[C:4]([Cl:3])[CH:5]=[CH:6][C:7]=2[F:39])=[CH:11][CH:12]=1)[NH:18][C:19]([C:21]1[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[CH:22]=1)=[O:20]Participants
5
Reactant 4
Product 1
Conditions
- Temperature
- 50 °C
Procedure
Ethane, 1-bromo-2-methoxy (5.7 mL, 0.1 mmol) was added to a mixture of (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid (20.0 mg, 38 μmol) and Et3N (13.2 μL, 0.1 mmol) in acetone (1.0 mL, 14 mmol), and resulting mixture was stirred at 50° C. overnight. The mixture was concentrated, and the residue was dissolved in AcOH (1.5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (10.7 mg, purity 95.7%) as a TFA salt. MS m/z [M+H]+ calc'd for C29H26ClF2N3O6, 586.15. found 585.8.
Workup
- customresulting mixture
- concentrationThe mixture was concentrated
- dissolutionthe residue was dissolved in AcOH (1.5 mL)
- filtrationfiltered
- custompurified by reverse phase preparative HPLC
Sources & evidence
- ORD record
- ord-4673afd8f71a4d6e9168e8a516660024
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08871792B2
Reaction notes
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