Pyridine-3-sulfonyl chloride → methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(pyridine-3-sulfonamido)butan-2-yl)piperidin-3-yl)acetate

HRID 932138Notes

Reaction equation

HRID 932138 reaction equation
[NH2:1][CH2:2][C@@H:3]([N:6]1[C@H:11]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C@@H:10]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[CH2:9][C@@:8]([CH2:27][C:28]([O:30][CH3:31])=[O:29])([CH3:26])[C:7]1=[O:32])[CH2:4][CH3:5].[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([S:39](Cl)(=[O:41])=[O:40])[CH:34]=1>N1C=CC=CC=1>[Cl:25][C:21]1[CH:20]=[C:19]([C@@H:10]2[C@@H:11]([C:12]3[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=3)[N:6]([C@@H:3]([CH2:4][CH3:5])[CH2:2][NH:1][S:39]([C:35]3[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=3)(=[O:41])=[O:40])[C:7](=[O:32])[C@:8]([CH2:27][C:28]([O:30][CH3:31])=[O:29])([CH3:26])[CH2:9]2)[CH:24]=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 3164136Pyridine-3-sulfonyl chlorideHCID 58573400Methyl 2-((3R,5R,6S)-1-((S)-1-aminobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate

Product 1

HCID 68000077methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(pyridine-3-sulfonamido)butan-2-yl)piperidin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of methyl 2-((3R,5R,6S)-1-((S)-1-aminobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate (13 mg, 0.027 mmol; Example 196, Step A) and pyridine-3-sulfonyl chloride (4.84 mg, 0.027 mmol) in pyridine (0.3 mL) was stirred at 110° C. for 4 h. Chromatography on silica gel (0 to 60% EtOAc in hexanes) gave methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-(pyridine-3-sulfonamido)butan-2-yl)piperidin-3-yl)acetate. This was hydrolyzed with LiOH (1N solution in water, 0.3 mL) in ethanol (0.5 mL) for 3 h at rt. HPLC purification (C18 column, eluted with 10 to 95% CH3CN in water, with 0.1% TFA) gave the title compound as a 1:1 complex with 2,2,2-trifluoroacetic acid.

Sources & evidence

ORD record
ord-6e389c704c6c4735845958737cddcca0
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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