Sulfuryl chloride → 1-[4-(5-cyano-1-methanesulfonylindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(R)-carboxylic acid
Reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:7]=[C:6]2[CH:16]1[CH2:21][CH2:20][N:19]([S:22](Cl)(=[O:24])=[O:23])[CH2:18][CH2:17]1)#[N:2].S(Cl)(Cl)(=O)=O.C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[NH:41]1[CH2:49][CH2:48][CH2:47][CH2:46][C@@H:42]1[C:43]([OH:45])=[O:44]>>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:7]=[C:6]2[CH:16]1[CH2:21][CH2:20][N:19]([S:22]([N:41]2[CH2:49][CH2:48][CH2:47][CH2:46][C@@H:42]2[C:43]([OH:45])=[O:44])(=[O:24])=[O:23])[CH2:18][CH2:17]1)#[N:2]Participants
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)-carboxamnide 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-methanesulfonyl-indol-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-ef5efabc5be845e8aa721dae8eb0c87a
- Source dataset
- uspto-grants-2000_10
- Patent number
- US06130220
Reaction notes
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