Water → HCID 18727254, compound

HRID 843025Notes

Reaction equation

HRID 843025 reaction equation
[CH2:1]([O:8][NH:9][C:10]([C@H:12]1[CH2:17][NH:16][CH2:15][CH2:14][N:13]1[S:18]([N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([F:36])[CH:34]=3)[N:29]([S:37]([CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])(=[O:39])=[O:38])[CH:28]=2)[CH2:23][CH2:22]1)(=[O:20])=[O:19])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:52]1([CH2:55]Br)[CH2:54][CH2:53]1.O>CN(C=O)C>[CH2:1]([O:8][NH:9][C:10]([C@H:12]1[CH2:17][N:16]([CH2:55][CH:52]2[CH2:54][CH2:53]2)[CH2:15][CH2:14][N:13]1[S:18]([N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([F:36])[CH:34]=3)[N:29]([S:37]([CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])(=[O:39])=[O:38])[CH:28]=2)[CH2:23][CH2:22]1)(=[O:19])=[O:20])=[O:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 18727255HCID 18727255, compound

Product 1

HCID 18727254HCID 18727254, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-benzyloxy-1-{4-[5-fluoro-1-(2-trimethylsilylethane-sulfonyl)indol-3-yl]piperidine-1-sulfonyl}piperazine-2-(R)-carboxamide (424 mg, 0.68 mmol) [prepared by proceeding as described in Example 15, Steps 4 and 5, but substituting 4-(4,5,6,7-tetra-fluoroindol-3-yl)piperidinesulfamoyl chloride with 4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidinesulfamoyl chloride] in DMF (3 ml) was added potassium carbonate (470 mg, 3.4 mmol) and cyclopropylmethyl bromide (101 mg, 0.75 mmol) and the suspension was vigorously stirred at RT for 24 h. Water was added and the reaction was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed (SiO2, PTLC, 50% ethyl acetate/hexanes) to give N-benzyloxy-1-{4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)indol-3-yl]piperidine-1-sulfonyl}-4-cyclopropylmethylpiperazine-2-(R)-carboxamide as a pale yellow oil. This material was converted to N-hydroxy-1-[4-(5-fluoroindol-3-yl)piperidine-1-sulfonyl]-4-cyclopropylmethylpiperazine-2-(R)-carboxamide by proceeding as described in Example 20, Step 2.

Workup

  1. extractionthe reaction was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed (SiO2, PTLC, 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1d838751212044c3b732fcf6f60eaf87
Source dataset
uspto-grants-2002_04
Patent number
US06376506B1

Reaction notes

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