Propanoyl bromide, 2-bromo- → 2-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide

HRID 2244526Notes

Reaction equation

HRID 2244526 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:29])[N:5]([CH:12]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=1)[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:6]2=[O:11].[Br:30][CH:31]([CH3:35])[C:32](Br)=[O:33].C(=O)(O)[O-].[Na+]>C(Cl)Cl.[Cl-].[Na+].O.CCOCC>[Br:30][CH:31]([CH3:35])[C:32]([NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:29])[N:5]([CH:12]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH3:28])[CH:19]=1)[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[C:6]2=[O:11])=[O:33]

Participants

7

Reactant 3

HCID 79047Propanoyl bromide, 2-bromo-2×HCID 516892Sodium BicarbonateHCID 98449131H-Isoindole-1,3(2H)-dione, 4-amino-2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-

Product 1

HCID 187583882-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamideYield 76%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 4-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione (500 mg, 1.20 mmol) and 2-bromopropionyl bromide (0.140 mL, 1.34 mmol) in methylene chloride (10 mL) was stirred at room temperature overnight. An additional 0.1 mL of 2-bromopropionyl bromide (1 mol) was added and the mixture stirred overnight. To the mixture was added brine (4 mL), Sodium bicarbonate (sat, 10 mL) and methylene chloride (15 mL). The organic layer was separated, was washed with brine (10 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give a yellow oil. The oil was slurried in ether (10 mL). The resulting suspension was filtered and the solid washed with ether to give 2-bromo-N-{2-[1-(3ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide as a white solid (500 mg, 76% yield): 1H NMR (CDCl3) δ 1.46 (t, J=6.9 Hz, 3H, CH3), 1.97 (d, J=6.9 Hz, 3H, CH3), 2.86 (s, 3H, CH3), δ 3.75 (dd, J=4.5. 14.4 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.49-4.59 (m, 2H, CHH, CH), 4.09(q, J=6.9 Hz, 2H, CH2), 5.87 (dd, J=4.4, 10.3 Hz, 1H, NCH), 6.82-6.85 (m, 1H, Ar), 7.09-7.13 (m, 2H, Ar), 7.53 (d, J=7.3 Hz, 1H, Ar), 7.68 (t, J=7.5 Hz, 1H, Ar), 8.73 (d, J=8.4 Hz, 1H, Ar), 10.19 (s, 1H, NH); 13C NMR (CDCl3) δ 14.61, 22.42, 41.54, 43.78, 48.67, 54.44, 55.87, 64.45, 111.39, 112.3, 116.10, 116.79, 120.35, 124.76, 129.14, 131.13, 136.02, 136.82, 148.55, 149.70, 167.28, 168.42, 169.11.

Workup

  1. customThe organic layer was separated
  2. washwas washed with brine (10 mL)
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was removed in vacuo
  5. customto give a yellow oil
  6. filtrationThe resulting suspension was filtered
  7. washthe solid washed with ether

Sources & evidence

ORD record
ord-ec020814c0f04fcbac0636ca11b7aeb2
Source dataset
uspto-grants-2010_03
Patent number
US07678825B2

Reaction notes

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