Thiomorpholine 1,1-dioxide → 6-chloro-4'-(3-chlorophenyl)-1'-[3-(1,1-dioxo-thiomorpholin-4-yl)-propyl]-2'-(5-fluoro-2-methylphenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728019Notes

Reaction equation

HRID 1728019 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:36])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[N:12]([CH2:24][CH2:25][CH2:26]Cl)[CH:11]3[C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=3[CH3:35])[C:5]2=[CH:4][CH:3]=1.[CH3:37]OC([Si](C)(C)C)C.[NH:45]1[CH2:50][CH2:49][S:48](=[O:52])(=[O:51])[CH2:47][CH2:46]1>FC(F)(F)C(O)=O>[CH3:25][CH2:24][N:12]([CH:11]([CH3:10])[CH3:28])[CH:13]([CH3:14])[CH3:37].[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:36])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[N:12]([CH2:24][CH2:25][CH2:26][N:45]4[CH2:50][CH2:49][S:48](=[O:52])(=[O:51])[CH2:47][CH2:46]4)[CH:11]3[C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=3[CH3:35])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6484228Thiomorpholine 1,1-dioxideHCID 775807906-Chloro-4'-(3-chlorophenyl)-1'-(3-chloro-propyl)-2'-(5-fluoro-2-methylphenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 2

HCID 81531DiisopropylethylamineHCID 743704596-chloro-4'-(3-chlorophenyl)-1'-[3-(1,1-dioxo-thiomorpholin-4-yl)-propyl]-2'-(5-fluoro-2-methylphenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 72.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

In a manner similar to the method described in example 60b, racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-1′-(3-chloro-propyl)-2′-(5-fluoro-2-methylphenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane prepared in example 60a (0.21 mg, 0.31 mmol) was reacted with thiomorpholin 1,1-dioxide (0.47 g, 3.48 mmol), trifluoroacetic acid (10 mL) and then N,N′-diisopropylethylamine (2 mL) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-1′-[3-(1,1-dioxo-thiomorpholin-4-yl)-propyl]-2′-(5-fluoro-2-methylphenyl)-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (72 mg, 36.2%).

Sources & evidence

ORD record
ord-e90ba999e77e45da8af93b22e1566f18
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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