4-Methylmorpholine → (2S)-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)butyl]benzenesulfonylamino}-3-methylbutyramide

HRID 1296559Notes

Reaction equation

HRID 1296559 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.CN1CCOCC1.[NH2:33][C@@H:34]([CH:38]([CH3:40])[CH3:39])[C:35]([NH2:37])=[O:36]>CN(C=O)C>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:33][C@@H:34]([CH:38]([CH3:40])[CH3:39])[C:35]([NH2:37])=[O:36])(=[O:24])=[O:23])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 445637ValinamideHCID 220544564-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)butyl]benzenesulfonyl chloride

Product 1

HCID 58912945(2S)-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)butyl]benzenesulfonylamino}-3-methylbutyramideYield 75.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)butyl]benzenesulfonyl chloride 13 (0.45 g, 1.19 mmol) was dissolved in dry DMF (5 mL), and added to a solution of N-methylmorpholine (3 mL) and (2S)-amino-3-methylbutyramide (0.18 g, 1.19 mmol) in DMF (10 mL). The reaction mixture was stirred at room temperature for 66 h. Solvent was removed by rotary evaporation and the residue was purified by flash silica gel chromatography eluting with chloroform/methanol/concentrated ammonium hydroxide (15:1:0.1, v/v) to give the desired product 14 as a white powder (0.41 g, 73% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.72 (d, 3H), 0.76 (d, 3H), 1.77 (m, 4H), 1.79 (m, 1H), 2.68 (m, 2H), 3.40 (m, 1H), 3.60 (m, 2H), 6.92 (s, 1H), 7.21 (s, 1H), 7.34 (d, 2H) 7.50 (d, 1H), 7.65 (d, 2H), 7.82 (m, 4H).

Workup

  1. customSolvent was removed by rotary evaporation
  2. customthe residue was purified by flash silica gel chromatography
  3. washeluting with chloroform/methanol/concentrated ammonium hydroxide (15:1:0.1

Sources & evidence

ORD record
ord-2a4c61f40c2544d89e695a8f5cc990e2
Source dataset
uspto-grants-2007_07
Patent number
US07247637B2

Reaction notes

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