3-(3,4-Dichlorophenyl)prop-2-enoic acid → HCID 68775491, compound

HRID 1174892Notes

Reaction equation

HRID 1174892 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[Cl:13])[CH:5]=[CH:6][C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH3:20][N:21]([CH3:37])[CH:22]1[CH2:26][CH2:25][N:24]([C:27]2[S:28][C:29]3[CH:35]=[C:34]([NH2:36])[CH:33]=[CH:32][C:30]=3[N:31]=2)[CH2:23]1>CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]([NH:36][C:34]2[CH:33]=[CH:32][C:30]3[N:31]=[C:27]([N:24]4[CH2:25][CH2:26][CH:22]([N:21]([CH3:37])[CH3:20])[CH2:23]4)[S:28][C:29]=3[CH:35]=2)=[O:9])[CH:10]=[CH:11][C:12]=1[Cl:13]

Participants

6

Reactant 3

HCID 145483-(3,4-Dichlorophenyl)prop-2-enoic acidHCID 65578Oxalyl chlorideHCID 632315072-(3-Dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine

Product 1

HCID 68775491HCID 68775491, compoundYield 32.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent4×

Procedure

Combine 3,4-dichlorocinnamic acid (0.083 g, 0.381 mmol), CH2Cl2 (5.0 mL), and DMF (3 drops) with stirring. Add oxalyl chloride (0.10 mL, 1.14 mmol) and stir the mixture for 3 h at room temperature. Concentrate the mixture in vacuo, add hexane (approximately 10 mL), re-concentrate in vacuo, and add CH2Cl2 (5.0 mL). Transfer the mixture to a 40 mL reaction vial and add a mixture of 2-(3-dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine (0.100 g, 0.381 mmol) (Example 1, step 3) in CH2Cl2 (5.0 mL). Shake the reaction vial overnight at room temperature. Dilute the reaction mixture with CH2Cl2 (30 mL), wash with saturated NaHCO3 (aqueous) (2×25 mL), dry over sodium sulfate, filter, and concentrate in vacuo. Purify the residue using silica gel chromatography (12 g column, 5-15% MeOH/CH2Cl2 over 45 min) to yield a yellow residue. Dilute the residue with CH2Cl2 (25 mL) and wash with 1 M NaOH (25 mL). Filter a yellow solid which precipitates in the separatory funnel. Concentrate the mother liquor in vacuo and filter, washing with cold CH2Cl2 to obtain a second crop. Combine the precipitate from the separatory funnel, and the second crop, to afford the title compound (57 mg, 32%). mass spectrum (m/e): 461.2 [M+1], 459.2 [M−1]. 1H NMR (400 MHz, CDCl3): δ8.31 (d, 1H, J=1.6 Hz), 7.65 (d, 1H, J=15.6 Hz), 7.64 (m, 1H), 7.52 (d, 1H, J=8.4 Hz), 7.46 (d, 1H, J=8.4 Hz), 7.37 (m, 1H), 7.35 (m, 1H), 7.16 (dd, 1H, J=8.8, 2.4 Hz), 6.53 (d, 1H, J=15.6 Hz), 3.86 (t, 1H, J=9.2 Hz), 3.74 (t, 1H, J=9.2 Hz), 3.56 (m, 1H), 3.50-3.42 (m, 1H), 2.98 (m, 1H), 2.36 (s, 6H), 2.29 (m, 1H), 2.07 (m, 1H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd hexane (approximately 10 mL)
  3. concentrationre-concentrate in vacuo
  4. additionadd CH2Cl2 (5.0 mL)
  5. customTransfer the mixture to a 40 mL reaction vial
  6. additionadd
  7. customthe reaction vial overnight
  8. customat room temperature
  9. washwash with saturated NaHCO3 (aqueous) (2×25 mL)
  10. dry with materialdry over sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customPurify the residue
  14. customsilica gel chromatography (12 g column, 5-15% MeOH/CH2Cl2 over 45 min)
  15. customto yield a yellow residue
  16. washwash with 1 M NaOH (25 mL)
  17. filtrationFilter a yellow solid which
  18. customprecipitates in the separatory funnel
  19. concentrationConcentrate the mother liquor in vacuo
  20. filtrationfilter
  21. washwashing with cold CH2Cl2
  22. customto obtain a second crop

Sources & evidence

ORD record
ord-6a028a7a3b784b56afaccabc7a992003
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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