Dimethylcarbamoyl Chloride → HCID 67418863, compound

HRID 1727443Notes

Reaction equation

HRID 1727443 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H: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])[CH2:7]2.[CH3:29][N:30]([CH3:34])[C:31](Cl)=[O:32]>>[CH2:27]([O:26][C:20]1[CH:19]=[C:18]([C@H:12]([N:8]2[C:9](=[O:11])[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[NH:1][C:31](=[O:32])[N:30]([CH3:34])[CH3:29])[CH2:7]2)[CH2:13][S:14]([CH3:17])(=[O:15])=[O:16])[CH:23]=[CH:22][C:21]=1[O:24][CH3:25])[CH3:28]

Participants

3

Reactant 2

HCID 6598Dimethylcarbamoyl ChlorideHCID 66718531(S)-7-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)isoindolin-1-one

Product 1

HCID 67418863HCID 67418863, compoundYield 49.1%

Procedure

A mixture of (1S)-7-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (0.5 g, 1.2 mmol) and dimethylcarbamyl chloride (0.6 mL, 6.5 mmol) was heated to reflux for 2 hours. The solvent was removed in vacuo. The residue was extracted with methylene chloride (50 mL) and sodium hydrogen carbonate (sat, 50 mL). The organic layer was washed with brine (50 mL) and dried over MgSO4. The solvent was removed in vacuo, and the residue was purified with prep HPLC to give (1S)-3-(2-[1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3,dihydro-1H-isoindol-4-yl}-1,1-dimethyl-urea as a white solid (280 mg, 48% yield): mp 170-172° C.; 1H NMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH3), 2.91 (s, 3H, CH3), 3.11 (s, 6H, 2 CH3), 3.70 (dd, J=5, 15Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.08 (q, J=7 Hz, 2H, CH2), 4.16-4.25 (m, 2H, CHH, NCHH), 4.41 (d, J=17Hz, 1H, NCHH), 5.69 (dd, J=5, 10 Hz, 1H, NCH), 6.83-6.95 (m, 4H, Ar), 7.43 (t, J=8 Hz, 1H, Ar), 8.33 (d, J=8Hz, 1H, Ar), 9.85 (s, 1H, NH); 13C NMR(CDCl3) δ 14.71, 3.32, 41.50, 48.06, 51.89, 55.99, 56.16, 64.65, 131.62, 112.30, 115.09, 116.63, 116.77, 119.34, 129.51, 133.68, 139.67, 141.19, 148.93, 149.80, 155.31, 170.64. Analy. Calculated for C23H29N3O6S+1 H2O: C 55.97; H 6.33; N 8.51; H2O 3.65. Found: C 55.57; H 6.02; N 8.44; H2O, 2.97.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 hours
  3. customThe solvent was removed in vacuo
  4. extractionThe residue was extracted with methylene chloride (50 mL) and sodium hydrogen carbonate (sat, 50 mL)
  5. washThe organic layer was washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified with prep HPLC

Sources & evidence

ORD record
ord-023f935c35fa472596217e923e03d2b3
Source dataset
uspto-grants-2009_02
Patent number
US07495112B2

Reaction notes

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