Water → 2-amino-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindolin-4-yl}acetamide

HRID 433283Notes

Reaction equation

HRID 433283 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:33])[N:9]([CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:10]2=[O:15])=[O:4].[N-:34]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>CC(C)=O.CCOCC>[NH2:34][CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:33])[N:9]([CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:10]2=[O:15])=[O:4]

Participants

7

Reactant 4

HCID 962Water2×HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 187583732-chloro-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindolin-4-yl}acetamide

Product 1

HCID 187583622-amino-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindolin-4-yl}acetamideYield 86.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 2-chloro-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindolin-4-yl}acetamide (0.30 g, 0.61 mmol) and sodium azide (90 mg, 1.38 mmol) in acetone (10 mL) was heated to reflux for 8 hours. To the solution was added triphenylphosphine (0.30 g, 1.1 mmol) and water (0.4 mL). The solution was heated to reflux for 5 more h. The solvent was removed in vacuo to give an oil. The oil was stirred in ether (10 mL) and water (10 mL) overnight to give a suspension. The suspension was filtered and washed with ether and water to give 2-amino-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindolin-4-yl}acetamide as a yellow solid (250 mg, 86% yield); mp, 111-112° C.; 1H NMR (CDCl3) δ1.48 (t, J.=6.9 Hz, 3H, CH3), 1.74 (brs, 2H, NH2), 2.86 (s, 3H, CH3), 3.57 (s, 2H, CH2), 3.77 (dd, J=4.6, 14.5 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.11 (q, J=7.0 Hz, 2H, CH2), 4.56 (dd, J=10.2, 14.2 Hz, 1H, CHH), 5.89 (dd, J=4.6, 10.2 Hz, 1H, NCH), 6.82-6.85 (m, 1H, Ar), 7.12-7.15 (m, 2H, Ar), 7.52 (d, J=7.2 Hz, 1H, Ar), 7.67 (t, J=7.5 Hz, 1H, Ar), 8.86 (d, J=8.3 Hz, 1H, Ar), 11.21 (s, 1H, NH); 13C NMR (CDCl3) δ14.68, 41.51, 48.65, 54.69, 55.88, 64.49, 111.45, 112.50, 115.81, 118.24, 120.37, 124.94, 129.38, 131.29, 135.90, 136.88, 148.55, 149.68, 167.64, 168.83, 172.41; Anal Calcd for C22H25N3O7S: C, 55.57; H, 5.30; N, 8.84. Found: C, 55.46; H, 5.33; N, 8.35.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 8 hours
  3. temperatureThe solution was heated
  4. temperatureto reflux for 5 more h
  5. customThe solvent was removed in vacuo
  6. customto give an oil
  7. filtrationThe suspension was filtered
  8. washwashed with ether and water

Sources & evidence

ORD record
ord-0078672a93d84e3bb61954420dab7ef5
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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