Dimethylcarbamoyl Chloride → HCID 10324048, compound

HRID 1797256Notes

Reaction equation

HRID 1797256 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:29])=[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.[CH3:30][N:31]([CH3:35])[C:32](Cl)=[O:33]>>[Cl:29][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:32](=[O:33])[N:31]([CH3:35])[CH3:30])=[C:10]2[C:6]=1[CH2:7][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:15])=[O:16])[C:9]2=[O:11]

Participants

3

Reactant 2

HCID 6598Dimethylcarbamoyl ChlorideHCID 68689720HCID 68689720, compound

Product 1

HCID 10324048HCID 10324048, compoundYield 70%

Conditions

Temperature
100 °C

Procedure

To (1S)-7-amino-4-chloro-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (800 mg, 1.82 mmol) was added dimethylcarbamyl chloride (3 ml). The mixture was heated at 100° C. for 20 hrs. The reaction mixture was cooled to room temperature and extracted with water (50 ml) and EtOAc (50 ml). The organic layer was washed with water (50 ml), brine (25 ml), dried over Na2SO4 and concentrated. The resulted oil was purified by chromatography to give (1S)-3-{7-chloro-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 (600 mg, 70% yield): mp, 205–207° C.; 1H NMR (CDCl3) δ 1.47 (t, J=7.0 Hz, 3H, OCH2CH3), 2.94 (s, 3H, CH3), 3.11 (s, 6H, N(CH3)2), 3.72 (dd, J=5, 15 Hz, 1H, CHHSO2), 3.88 (s, 3H, CH3), 4.05–4.22 (m, 4H, CHHSO2+CHHN+OCH2CH3), 4.40 (d, J=10 Hz, 1H, CHHN), 5.73–5.79 (m, 1H, NCH), 6.86–6.96 (m, 3H, Ar), 7.36 (d, J=9 Hz, 1H, Ar), 8.35 (d, J=9 Hz, 1H, Ar), 9.77 (s, 1H, NHCO); 13C NMR (CDCl3) δ 14.68, 36.27, 41.51, 46.96, 51.47, 55.73, 55.97, 64.64, 111.64, 111.67, 112.28, 118.20, 118.54, 119.31, 120.08, 129.13, 133.24, 138.58, 138.77, 148.94, 149.88, 155.01, 169.72. Anal Calcd for C23H28ClN3O6S: C, 54.32; H, 5.65; N, 8.12. Found: C, 54.16; H, 5.42; N, 7.82.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with water (50 ml) and EtOAc (50 ml)
  3. washThe organic layer was washed with water (50 ml), brine (25 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulted oil was purified by chromatography

Sources & evidence

ORD record
ord-754249ac4705450aa06eda6de53a99dd
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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