Dimethylformamide → HCID 86616141, compound

HRID 1787968Notes

Reaction equation

HRID 1787968 reaction equation
[NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9](OC)=[C:8]([O:14][CH2:15]C)[CH:7]=1)[CH2:3][C:4]#[N:5].CCN([CH2:22][CH3:23])CC.CO[C:26](=[O:42])[C:27]1[C:32]([NH:33][C:34]([CH:36]2[CH2:38][CH2:37]2)=[O:35])=[CH:31][CH:30]=[C:29]([Cl:39])[C:28]=1[CH2:40]Br.CN(C=[O:47])C>>[Cl:39][C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:34]([CH:36]2[CH2:37][CH2:38]2)=[O:35])=[C:27]2[C:28]=1[CH2:40][N:1]([CH:2]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:14][CH2:15][O:47][CH2:22][CH3:23])[CH:7]=1)[CH2:3][C:4]#[N:5])[C:26]2=[O:42]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 221771543-Amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrileHCID 669200082-Bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester

Product 1

HCID 86616141HCID 86616141, compoundYield 80%

Conditions

Temperature
90 °C

Procedure

To the DMF solution (20 ml) of 3-Amino-3-(3-ethoxy-4-methoxy-phenyl)-propionitrile (1.55 g, 7 mmol) was added Et3N (1.6 ml, 12 mmol) followed by 2-bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (2.42 g, 7 mmol). The mixture was heated at 90° C. for 12 hrs then cooled to room temperature. The mixture was extracted with EtOAc (50 ml) and water (50 ml). The organic layer washed with water (50 ml) and brine (50 ml), dried over Na2SO4 and concentrated in vacuo. The resulted oil was purified by silica gel chromatography to give cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxymethoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (2.4 g, 80%): mp 200-202° C.; 1H NMR (CDCl3) δ 0.90-0.94 (m, 2H, c-CH2), 1.09-1.14 (m, 2H, c-CH2), 1.45 (t, J=7.0 Hz, 3H, CH3), 1.64-1.70 (m, 1H, c-CH), 3.12-3.32 (m, 2H, CH2CN), 3.89 (s, 3H), 3.99-4.12 (m, 3H, OCH2CH3+CHHN), 4.37 (d, J=18 Hz, 1H. CHHN), 5.62-5.68 (m, 1H, NCH), 6.87-6.98 (m, 3H, Ar), 7.40 (d, J=9 Hz, 1H, Ar), 8.47 (t, J=9 Hz, 1H, Ar), 10.34 (s, 1H, NH); 13C NMR (CDCl3) δ 8.5, 14.7, 16.2, 21.2, 46.4, 51.8, 56.0, 64.7, 111.7, 112.2, 116.9, 118.4, 119.1, 119.8, 121.9, 127.9, 133.3, 136.9, 138.9, 149.9, 150.0, 169.0, 172.7; Anal Calcd for C24H24ClN3O4: C, 63.50; H, 5.33; N, 9.26. Found: C, 63.43; H, 5.31; N, 9.01

Workup

  1. temperaturethen cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (50 ml) and water (50 ml)
  3. washThe organic layer washed with water (50 ml) and brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulted oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3976d1dd1f7b491f96647de6073f7480
Source dataset
uspto-grants-2009_03
Patent number
US07511072B2

Reaction notes

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