3-(p-Tolyl)acrylic acid → HCID 68773963, compound

HRID 1174890Notes

Reaction equation

HRID 1174890 reaction equation
[CH3:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([OH:10])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:19][N:20]([CH3:36])[CH:21]1[CH2:25][CH2:24][N:23]([C:26]2[S:27][C:28]3[CH:34]=[C:33]([NH2:35])[CH:32]=[CH:31][C:29]=3[N:30]=2)[CH2:22]1>CN(C=O)C.C(Cl)Cl>[CH3:19][N:20]([CH3:36])[CH:21]1[CH2:25][CH2:24][N:23]([C:26]2[S:27][C:28]3[CH:34]=[C:33]([NH:35][C:8](=[O:10])[CH:7]=[CH:6][C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:12][CH:11]=4)[CH:32]=[CH:31][C:29]=3[N:30]=2)[CH2:22]1

Participants

6

Reactant 3

HCID 158353-(p-Tolyl)acrylic acidHCID 65578Oxalyl chlorideHCID 632315072-(3-Dimethylamino-pyrrolidin-1-yl)-benzothiazol-6-ylamine

Product 1

HCID 68773963HCID 68773963, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

Combine 4-methylcinnamic acid (0.093 g, 0.572 mmol), CH2Cl2 (5.0 mL), and DMF (3 drops) with stirring. Add oxalyl chloride (0.17 mL, 1.91 mmol) and stir the mixture for 2.5 h at room temperature. Concentrate the mixture in vacuo, add hexane (approximately 10 mL), re-concentrate in vacuo, and add CH2Cl2 (4.0 mL). Transfer the mixture to a 40 mL reaction vial and add a solution 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 for 1 h at room temperature. Dilute the reaction mixture with CH2Cl2 (25 mL), wash with aqueous 1.0 M NaOH (50 mL), concentrate in vacuo, and purify using silica gel chromatography (12 g column, 10-20% MeOH/CH2Cl2 for 16 min.) to afford the title compound as a yellow solid (96 mg, 62%). mass spectrum (m/e): 407.3 [M+1], 405.2 [M−1]. 1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 7.71 (d, 1H, J=15.6 Hz), 7.67 (s, 1H), 7.50 (d, 1H, J=9.2 Hz), 7.39 (d, 2H, J=7.2 Hz), 7.13-7.19 (m, 3H), 6.51 (d, 1H, J=15.6 Hz), 3.82 (t, 1H, J=8.0 Hz), 3.71 (t, 1H, J=9.2 Hz), 3.53 (m, 1H), 3.39 (t, 1H, J=8.0 Hz), 2.89 (m, 1H), 2.36 (s, 3H), 2.30 (s, 6H), 2.25 (m, 1H), 1.99 (m, 1H).

Workup

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd hexane (approximately 10 mL)
  3. concentrationre-concentrate in vacuo
  4. additionadd CH2Cl2 (4.0 mL)
  5. customTransfer the mixture to a 40 mL reaction vial
  6. customShake the reaction vial for 1 h at room temperature
  7. washwash with aqueous 1.0 M NaOH (50 mL)
  8. concentrationconcentrate in vacuo
  9. custompurify
  10. customsilica gel chromatography (12 g column, 10-20% MeOH/CH2Cl2 for 16 min.)

Sources & evidence

ORD record
ord-1bb356e059734281ac3edd58d5a11ec0
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

Loading…