N,O-Dimethylhydroxylamine → 1-({5-[(diallylamino)methyl]thien-2-yl}sulfonyl)-N-methoxy-N-methylpiperidine-4-carboxamide

HRID 906643Notes

Reaction equation

HRID 906643 reaction equation
[CH2:1]([N:4]([CH2:8][C:9]1[S:13][C:12]([S:14]([N:17]2[CH2:22][CH2:21][CH:20]([C:23](OC)=[O:24])[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:11][CH:10]=1)[CH2:5][CH:6]=[CH2:7])[CH:2]=[CH2:3].[CH3:27][NH:28][O:29][CH3:30].C([Mg]Cl)(C)C>C1COCC1>[CH2:1]([N:4]([CH2:8][C:9]1[S:13][C:12]([S:14]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]([N:28]([O:29][CH3:30])[CH3:27])=[O:24])[CH2:19][CH2:18]2)(=[O:15])=[O:16])=[CH:11][CH:10]=1)[CH2:5][CH:6]=[CH2:7])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 14232N,O-DimethylhydroxylamineHCID 67403857Methyl 1-({5-[(diallylamino)methyl]thien-2-yl}sulfonyl)piperidine-4-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 867613991-({5-[(diallylamino)methyl]thien-2-yl}sulfonyl)-N-methoxy-N-methylpiperidine-4-carboxamideYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

327a (390 mg, 1 mmol) and N,O-dimethylhydroxylamine (148 mg, 1.52 mmol) were stirred at −20° C. in anhydrous THF, while Isopropylmagnesium chloride in THF (2M, 1.65 mL, 3.23 mmol) were slowly added. The reaction mixture was allowed to warm to r.t. during 30′, followed by an additional stirring at r.t. for 30′. The reaction is quenched with ammoniumchloride solution (20%). The aqueous layer is extracted with t-butylmethylether, and the combined organic layers are washed with brine, dried over MgSO4 and evaporated to dryness. The crude is purified by flash chromatography on silica gel using cyclohexan/EtOAc 1:1 as eluent. 327b (380 mg, 90%) was obtained as a colourless solid: H1 NMR (DMSO d6) δ7.53 (d, J=3.7 Hz, 1H), 7.16 (d, J=3.6 1H), 5.89 (m, 2H), 5.24 (m, 4H), 3.86 (s, 2H), 3.62 (m, 5H), 3.15 (m, 7H), 2.74 (m, 1H), 2.50 (m, 2H), 2.25 (m, 2H), 1.84 (m, 2H), 1.63 (m, 2H). M/Z APCI: 428.1 (M+1).

Workup

  1. additionwere slowly added
  2. customThe reaction is quenched with ammoniumchloride solution (20%)
  3. extractionThe aqueous layer is extracted with t-butylmethylether
  4. washthe combined organic layers are washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated to dryness
  7. customThe crude is purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-2eb64060d63f40a8aa28df90d6cb0309
Source dataset
uspto-grants-2011_09
Patent number
US08012995B1

Reaction notes

Loading…