Sulfuryl chloride → 1-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(R)-carboxylic acid

HRID 843022Notes

Reaction equation

HRID 843022 reaction equation
ON[C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[S:11]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:29]#[N:30])[CH:27]=3)[N:22]([S:31]([CH3:34])(=[O:33])=[O:32])[CH:21]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12])=[O:4].C(C1C=C2C(=CC=1)N(S(C)(=O)=[O:47])C=C2C1CCN(S(Cl)(=O)=O)CC1)#N.S(Cl)(Cl)(=O)=O.C([C@@H]([C@H](C(O)=O)O)O)(O)=O.N1CCCC[C@@H]1C(O)=O>>[C:29]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[N:22]([S:31]([CH3:34])(=[O:33])=[O:32])[CH:21]=[C:20]2[CH:17]1[CH2:16][CH2:15][N:14]([S:11]([N:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C@@H:5]2[C:3]([OH:47])=[O:4])(=[O:12])=[O:13])[CH2:19][CH2:18]1)#[N:30]

Participants

5

Reactant 4

HCID 24648Sulfuryl chlorideHCID 15611388(r)-Pipecolinic acid (l)-tartrate saltHCID 15871790N-hydroxy-1-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]-piperidine-2-(R)-carboxamideHCID 226158104-(5-Cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl chloride

Product 1

HCID 187272161-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(R)-carboxylic acidYield 86%

Procedure

10% Palladium on carbon (0.49 g) was added to a solution of 1-benzyloxycarbonyl-4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine (0.98 g, 2.24 mmol) [prepared as described in Step 2 above] in 80% ethanol/tetrahydrofuran (10 ml) under an argon atmosphere. The reaction mixture was stirred under an atmosphere of hydrogen gas (1 atm) for 2 h. The reaction mixture was degassed, filtered through Celite and concentrated in vacuo to give 4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine (97%) as a white solid. This material was converted to N-hydroxy-1-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]-piperidine-2-(R)-carboxamide by converting it to 4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl chloride by following Example 16, Step 1, coupling the sulfonyl chloride with (R)-pipecolinic acid (L)-tartrate salt to give 1-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(R)-carboxylic acid (86%) by following Example 14, Step 6 and then converting the acid to the final compound by following Example 16, Steps 3 and 5; mp: 143.3-143.9° C.

Sources & evidence

ORD record
ord-268153cf2eae48359de7c6dd03f2851f
Source dataset
uspto-grants-2002_04
Patent number
US06376506B1

Reaction notes

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