4-Aminobenzonitrile → acetic acid rac-3-[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-5'-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidin]-2'-yl]-2,2-dimethyl-propyl ester
Reaction equation
FC(F)(F)C(O)=O.[C:8]([O:11][CH2:12][C:13]([CH3:42])([CH3:41])[CH2:14][CH:15]1[C:19]2([C:27]3[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=3)[NH:21][C:20]2=[O:29])[CH:18]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=2[F:37])[CH:17]([C:38]([OH:40])=O)[NH:16]1)(=[O:10])[CH3:9].C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[NH2:67][C:68]1[CH:75]=[CH:74][C:71]([C:72]#[N:73])=[CH:70][CH:69]=1>>[Cl:28][C:24]1[CH:23]=[C:22]2[NH:21][C:20](=[O:29])[C@:19]3([C@@H:18]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=4[F:37])[C@H:17]([C:38](=[O:40])[NH:67][C:68]4[CH:75]=[CH:74][C:71]([C:72]#[N:73])=[CH:70][CH:69]=4)[NH:16][C@H:15]3[CH2:14][C:13]([CH3:42])([CH3:41])[CH2:12][O:11][C:8](=[O:10])[CH3:9])[C:27]2=[CH:26][CH:25]=1Participants
5
Reactant 4
Product 1
Procedure
In a manner similar to the method described in Example 5, rac-(2′S,3′R,4′S,5′R)-2′-(3-acetoxy-2,2-dimethyl-propyl)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid prepared in Example 103 (0.25 g, 0.4 mmol), was reacted with diisopropylethylamine (0.47 g, 3.6 mmol), diphenylphosphinic chloride (0.38 g, 1.6 mmol), then reacted with 4-aminobenzonitrile (Aldrich) (0.19 g, 1.6 mmol) to give acetic acid rac-3-[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-5′-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidin]-2′-yl]-2,2-dimethyl-propyl ester as a light yellow foam (Yield 0.1 g, 40%).
Sources & evidence
- ORD record
- ord-f53dbd0c66bb477698b83dcc7890c349
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08088815B2
Reaction notes
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