Morpholine → 6-chloro4'-(3-chlorophenyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-1'-(3-morpholin-4-yl-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728023Notes

Reaction equation

HRID 1728023 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[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[C:33]([O:34][CH:35]([CH3:37])[CH3:36])=[CH:32][CH:31]=[C:30]([F:38])[C:29]=3[F:39])[C:5]2=[CH:4][CH:3]=1.[CH3:41]OC([Si](C)(C)C)C.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>FC(F)(F)C(O)=O>[CH3:25][CH2:24][N:12]([CH:11]([CH3:10])[CH3:28])[CH:13]([CH3:14])[CH3:41].[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:40])[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:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[CH:11]3[C:28]3[C:33]([O:34][CH:35]([CH3:37])[CH3:36])=[CH:32][CH:31]=[C:30]([F:38])[C:29]=3[F:39])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 775806586-Chloro-4'-(3-chloro-phenyl)-1'-(3-chloro-propyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6'-dioxo spiro[indole-3,3'-piperidine] 1-methoxyethyl trimethylsilane

Product 2

HCID 81531DiisopropylethylamineHCID 743705376-chloro4'-(3-chlorophenyl)-2'-(2,3-difluoro-6-isopropoxy-phenyl)-1'-(3-morpholin-4-yl-propyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 55.6%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

In a manner similar to the method described in example 60b, racemic (2′S,3R,4′S)-6-chloro-4′-(3-chloro-phenyl)-1′-(3-chloro-propyl)-2′-(2,3-difluoro-6-isopropoxy-phenyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane prepared in example 73b (0.3 g, 0.41 mmol) was reacted with morpholine (10 mL), trifluoroacetic acid (10 mL) and then N,N′-diisopropylethylamine (1 mL) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(2,3-difluoro-6-isopropoxy-phenyl)-1′-(3-morpholin-4-yl-propyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (0.15 g, 55.6%).

Sources & evidence

ORD record
ord-03498ec7835f49f78dd6e7de0a0b68b2
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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