Diphenylphosphinic chloride → (2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid [4-(3-methanesulfonyl-propoxy)-2-methoxy-phenyl]amide

HRID 417341Notes

Reaction equation

FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]2[NH:15][C:16](=[O:38])[C@:17]3([C@@H:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=4[F:29])[C@H:20]([C:30](O)=[O:31])[NH:19][C@H:18]3[CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12]2=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[CH3:63][S:64]([CH2:67][CH2:68][CH2:69][O:70][C:71]1[CH:76]=[CH:75][C:74]([NH2:77])=[C:73]([O:78][CH3:79])[CH:72]=1)(=[O:66])=[O:65]>>[CH3:63][S:64]([CH2:67][CH2:68][CH2:69][O:70][C:71]1[CH:76]=[CH:75][C:74]([NH:77][C:30]([C@@H:20]2[NH:19][C@@H:18]([CH2:33][C:34]([CH3:37])([CH3:35])[CH3:36])[C@:17]3([C:12]4[C:11](=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=4)[NH:15][C:16]3=[O:38])[C@H:21]2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=2[F:29])=[O:31])=[C:73]([O:78][CH3:79])[CH:72]=1)(=[O:65])=[O:66]

Participants

Reactant 4

HCID 73910Diphenylphosphinic chloride

HCID 81531Diisopropylethylamine

HCID 582862934-(3-Methanesulfonyl-propoxy)-2-methoxy-phenylamine

HCID 71723204(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid trifluoroacetic acid

Product 1

HCID 58286353(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid [4-(3-methanesulfonyl-propoxy)-2-methoxy-phenyl]amideYield 52.6%

Procedure

In a manner similar to the method described in Example 5, chiral (2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid trifluoroacetic acid prepared in Example 136 (0.2 g, 0.35 mmol), was reacted with diisopropylethylamine (0.22 g, 1.7 mmol), diphenylphosphinic chloride (0.16 g, 0.7 mmol), then reacted with 4-(3-methanesulfonyl-propoxy)-2-methoxy-phenylamine prepared in Example 180 (0.13 g, 0.5 mmol) to give chiral (2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid [4-(3-methanesulfonyl-propoxy)-2-methoxy-phenyl]amide as a yellow solid (Yield 0.13 g, 51%).

Sources & evidence

ORD record: ord-5ffa52815dbf4d1f8fc199e8d6839628
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088815B2

Reaction notes

Loading…