Pyridine → HCID 178472582, compound
Reaction equation
CN(C=O)C.CC#N.C(Cl)(=O)C(Cl)=O.[NH:15]1[C:19]([C:20]([O-:22])=O)=[N:18][N:17]=[N:16]1.[K+].[K+].N1C(C([O-])=O)=NN=N1.[CH2:33]([O:35][C:36](=[O:57])[C@H:37]([OH:56])[CH2:38][N:39]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[C:52]([Cl:54])[CH:51]=[CH:50][C:49]=2[F:55])=[CH:44][CH:43]=1)[NH2:40])[CH3:34].N1C=CC=CC=1>>[CH2:33]([O:35][C:36](=[O:57])[C@H:37]([OH:56])[CH2:38][N:39]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([C:48]2[CH:53]=[C:52]([Cl:54])[CH:51]=[CH:50][C:49]=2[F:55])=[CH:46][CH:47]=1)[NH:40][C:20]([C:19]1[NH:18][N:17]=[N:16][N:15]=1)=[O:22])[CH3:34]Participants
Reactant 6
Product 1
Procedure
To a stirred solution of DMF (734 μL, 9.5 mmol) in MeCN (2 mL, 50 mmol) at 0° C., was slowly added a solution of oxalyl chloride (257 μL, 3.0 mmol) in MeCN (500 μL, 9 mmol). After 10 minutes, dipotassium 1H-tetrazole-5-carboxylate (249 mg, 1.3 mmol) was added and after stirring for a further 15 minutes, was added to a solution of (R)-3-[N-(5′-chloro-2′-fluoro-biphenyl-4-ylmethyl)-hydrazino]-2-hydroxy-propionic acid ethyl ester (300 mg, 0.8 mmol) in MeCN (2 mL, 40 mmol) and pyridine (661 μL, 8.2 mmol). The mixture was stirred at 0° C. for 10 minutes then evaporated under reduced pressure and purified (Interchim reverse phase chromatography column; elute from 55-75%, both peaks coeluted together) to yield the title compound (280 mg). A portion (80 mg) was further purified by preparative HPLC to yield the title compound as a TFA salt (33 mg; purity 98%). MS m/z [M+H]+ calc'd for C20H20ClFN6O4, 463.12. found 463.4.
Workup
- stirringThe mixture was stirred at 0° C. for 10 minutes
- customthen evaporated under reduced pressure
- custompurified (Interchim
- washelute from 55-75%
Sources & evidence
- ORD record
- ord-1fc40bc0dcc140c18246bbea44950231
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09120758B2
Reaction notes
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